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  • 1
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    Transmucosal Absorption Enhancers in the Drug Delivery Field (2021)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2023-12-21
    Description: Development of strategies to assist the movement of poorly permeable molecules across biological barriers has long been the goal of drug delivery science. In the last three decades, there has been an exponential increase in advanced drug delivery systems that aim to address this issue. However, most proprietary delivery technologies that have progressed to clinical development are based on permeation enhancers (PEs) that have a history of safe use in man. This Special Issue entitled “Transmucosal Absorption Enhancers in the Drug Delivery Field” aims to present the current state-of-the-art in the application of PEs to improve drug absorption. Emphasis is placed on identification of novel permeation enhancers, mechanisms of barrier alteration, physicochemical properties of PEs that contribute to optimal enhancement action, new delivery models to assess PEs, studies assessing safety of PEs, approaches to assist translation of PEs into effective oral, nasal, ocular and vaginal dosage forms and combining PEs with other delivery strategies.
    Keywords: R5-920 ; RM1-950 ; chitosan ; intestinal epithelial cells ; ocular delivery ; amphiphilic polymers ; cornea ; tight junction modulator ; cyclodextrin ; permeability ; gemini surfactant ; transferrin ; compound 48/80 ; epithelial permeability ; cervicovaginal tumors ; nanoparticles ; confocal laser scanning microscopy ; safety ; formulation ; salcaprozate sodium ; intestinal absorption ; FITC-dextran ; curcumin ; block copolymers ; nasal vaccination ; whole leaf ; brush border ; ocular drug delivery ; vaccine adjuvant ; nanoparticle ; nasal delivery ; efflux ; permeation enhancers ; absorption enhancers ; nose to brain delivery ; small intestine ; epithelium ; CNS disorders ; absorption modifying excipients ; insulin ; absorption enhancer ; gel ; intestinal delivery ; thermogel system ; Caco-2 ; biocompatibility studies ; absorption enhancement ; man ; PN159 ; poorly absorbed drug ; tryptophan ; tight junction ; oral macromolecule delivery ; penetration enhancer ; intestinal permeation enhancers ; nanocrystals ; simvastatin ; nanomedicine ; enterocyte ; N-dodecyl-?-D-maltoside (DDM) ; cell-penetrating peptide ; quaternization ; KLAL ; nasal ; nasal permeability ; transmucosal drug delivery ; Caco-2 cells ; mast cell activator ; penetration enhancers ; drug delivery ; nose-to-brain ; bioenhancer ; polymeric micelles ; mucoadhesion ; cell-penetrating peptide (CPP) ; simulated intestinal fluid ; vaginal delivery ; nasal formulation ; pharmacokinetic interaction ; sodium caprate ; clinical trial ; transmucosal permeation ; drug absorption enhancer ; sugar-based surfactants ; nanocapsules ; imatinib ; teriparatide ; osteoporosis ; hydrophobization ; F-actin ; combined microsphere ; transepithelial electrical resistance ; oral delivery ; ocular conditions ; metabolism ; antimicrobial peptide ; permeation enhancer ; drug administration ; antiepileptic drug ; amino acid ; in vivo studies ; sodium cholate (NaC) ; epithelial transport ; preclinical ; nose to brain transport ; pharmacokinetics ; chitosan derivatives ; ophthalmology ; tight junctions ; sheep ; cationic functionalization ; GLP-1 ; pulmonary ; and liposome ; cytochrome P450 ; claudin ; P-glycoprotein ; in situ hydrogel ; mucoadhesiveness ; PTH 1-34 ; Aloe vera ; oral peptides ; bic Book Industry Communication::M Medicine
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  • 2
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    Model-Informed Precision Dosing (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2023-04-05
    Description: Model-informed precision dosing (MIPD) is an advanced quantitative approach focusing on individualized treatment optimization. MIPD integrates mathematical models of drugs and diseases combined with individual patient characteristics (e.g., genotype, anthropometric factors, and organ function). MIPD has been highlighted as a useful tool for drug dosage selection in both the drug development process and clinical practice and it is a rapidly growing discipline that is supported by the main drug regulatory agencies. Despite the potential benefits of this methodology toward personalized medicine, its application is still limited. The Special Issue presented here includes several PKPD and PBPK models focused on improving the current state of art regarding the PK behaviour of different drugs with the aim of improving the efficacy/safety balance of these treatments and their clinical outcome; the Special Issue is intended to be of particular interest for clinical pharmacologists, pharmacometricians, and specific clinicians who routinely use the considered drugs.
    Keywords: model-informed precision dosing (MIPD) ; efficacy PKPD indexes ; pharmacokinetics ; pharmacodynamics ; PKPD modeling and simulation ; dosing algorithms ; nomograms ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KND Manufacturing industries::KNDP Pharmaceutical industries
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  • 3
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    Food Supplements and Functional Foods Assessment for Health and Nutrition (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2024-03-28
    Description: Nowadays, diet-related non-communicable diseases and their complications are one of the most important public health problems worldwide. Food supplements and functional foods are considered food products which contribute to the achievement of optimal nutritional well-being, health status, and quality of life through reducing the risk of diseases and promoting the appropriate function of human organs and systems. Nowadays, the assessment of these functional foods and the study of their implications in nutrition and health are important challenges in societies of developed countries where consumers increasingly demand foods with added value beyond the provision of nutrients and the satisfaction of appetite. In this reprint, the characterization of the nutritional composition and phytochemicals of functional foods and food supplements as well as the evaluation of their potential health benefits in different disorders and diseases through clinical trials or preliminary studies are addressed.
    Keywords: food supplement ; folic acid ; pregnancy ; food safety ; health claims ; nutrition ; Amazonian fruits ; composition ; metabolic effects ; royal jelly ; acetylcholine ; fatty acid ; ophthalmology ; dry eye ; magnesium ; pharmacy ; food supplements ; drugstore ; functional foods ; healthy eating ; credibility ; extrinsic attributes ; conjoint analysis ; Mediterranean diet ; phytonutrients ; dietary recommendations ; healthy diet ; polyphenols ; flavonoids ; carotenoids ; organosulfur ; caffeine ; antidiabetic activity ; antioxidant activity ; inhibition of α-glucosidase ; inhibition of α-amylase ; inhibition of collagenase ; kombucha ; bacteria ; yeast ; metagenome ; metabolome ; tea polyphenols ; antioxidants ; Glossogyne tenuifolia ; exercise ; forelimb grip strength ; lactate ; ammonia ; creatine kinase ; medium-chain triglycerides (MCTs) ; obesity ; energy expenditure ; diet-derived fat ; postprandial resting metabolism ; sedentary ; octanoic acid ; decanoic acid ; creatine ; magnetic resonance spectroscopy ; cost-effectiveness ; brain ; muscle ; healthcare ; anthocyanins ; organosulfur compounds ; tannins ; phenolic acids ; Persea americana ; non-alcoholic liver disease ; liver enzymes ; inflammation ; oxidative stress ; novel foods ; novel ingredients ; extracts ; risk assessment ; dietary supplements ; HPLC ; food authenticity ; neural tube defects ; food ; food analysis ; food ingredients ; infant formula ; kynurenic acid ; (poly)phenol-based supplement ; pharmacokinetics ; urinary excretion ; bioavailability ; inter-individual variability ; non-invasive brain stimulation ; TMS ; a-tDCS ; indicaxanthin ; brain food ; cortical excitability ; homeostatic plasticity ; trans-resveratrol ; regulation ; labels ; nutrition claims ; high-performance thin-layer chromatography ; HPTLC ; glutamine ; intestinal stem cells ; crypt ; proliferation ; burns ; micronutrient ; health claim ; labeling ; European legislation ; thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences ; thema EDItEUR::J Society and Social Sciences::JB Society and culture: general::JBC Cultural and media studies::JBCC Cultural studies::JBCC4 Cultural studies: food and society
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  • 4
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    Analytical Techniques in Pharmaceutical and Biomedical Analysis (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2023-04-05
    Description: This Special Issue is a collection of research topics on developing analytical and bioanalytical methods for isolation, identification, and determination of substances in biomedical and pharmaceutical matrices. Special attention is given to advancements in sample preparation, separation techniques and novel detection methods of small molecules, peptides, and monoclonal antibodies. The presented analytical methods exhibit several applications, including pharmacokinetic studies, therapeutic drug monitoring, microdialysis, toxicology, disease screening or drug stability study. Two comprehensive review articles were also presented on applying capillary electrophoresis to analyze bioactive compounds in herbal matrices.
    Keywords: CNS ; sulfasalazine ; brain to plasma ratio ; LC-ESI-TOF-MS ; rituximab ; quadripolar mass spectrometer ; albumin depletion ; pharmacokinetics ; orbitrap mass spectrometer ; IgG-immunocapture ; bubble-generating magnetic liposomes ; bionic membrane ; permeable compounds ; herbal medicines ; LC–MS ; capillary electrophoresis ; herbal ; raw material ; tea ; polyphenols ; flavonoids ; amino acids ; coumarins ; alkaloids ; chlorambucil and valproic acid ; HPLC-UV and GC-MS methods ; optimization and validation ; determination in plasma ; combined anticancer therapy ; herbal drugs ; medicinal plants ; quality control ; quantitative analysis ; pharmaceutical analysis ; 4-acetamidobenzoic acid ; validation ; pharmacokinetic ; pigs ; LC-MS/MS ; iron determination ; spectrophotometry ; flow analysis ; direct injection detector ; multi-pumping flow system ; medical errors ; hospital workflow ; patient safety ; Raman spectroscopy ; IV drugs ; piperacillin ; tazobactam ; non-invasively ; vildagliptin ; remogliflozin ; ratio derivative spectrophotometry ; determination ; formulation ; ecofriendly ; confidence interval ; stability ; retrospective analysis ; sample size ; regulatory bioanalysis ; bioanalytical method validation ; heparin ; metal–organic framework ; zeolite imidazolate framework-8 ; kinetic ; thermodynamic ; Oncheong-eum ; traditional herbal prescription ; method development ; method validation ; high-performance liquid chromatography ; thalassemia ; human hemoglobin ; wooden-tip electrospray ionization ; multiply charged ions ; mass spectrometry ; multiply charged ion ; GC–MS ; analytical QbD ; genotoxic impurity ; alkyl halide ; (Q)SAR ; analytical method development ; tyrosine kinase inhibitor ; liquid chromatography–mass spectrometry ; active metabolite ; therapeutic drug monitoring ; chronic lymphocytic leukemia ; assay error equation ; oral anticancer drug ; IWR-1-endo ; Wnt signaling inhibitor ; solid-phase extraction ; cerebral microdialysis ; bioanalysis ; Tafamidis ; polymorphs ; crystal structure ; powder diffraction ; thermal stability ; blood collection tubes ; citrate anticoagulant ; direct spectrometric determination ; quality control method ; anticoagulant concentration ; draw volume ; anticoagulant volume ; magnesium contamination ; potassium contamination ; Agrimonia pilosa ; apigenin-7-O-glucuronide ; cream ; HPLC-DAD ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PN Chemistry ; bic Book Industry Communication::P Mathematics & science::PN Chemistry::PNF Analytical chemistry
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  • 5
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    Regional Intestinal Drug Absorption (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2022-05-06
    Description: The gastrointestinal tract (GIT) can be broadly divided into several regions: the stomach, the small intestine (which is subdivided to duodenum, jejunum, and ileum), and the colon. The conditions and environment in each of these segments, and even within the segment, are dependent on many factors, e.g., the surrounding pH, fluid composition, transporters expression, metabolic enzymes activity, tight junction resistance, different morphology along the GIT, variable intestinal mucosal cell differentiation, changes in drug concentration (in cases of carrier-mediated transport), thickness and types of mucus, and resident microflora. Each of these variables, alone or in combination with others, can fundamentally alter the solubility/dissolution, the intestinal permeability, and the overall absorption of various drugs. This is the underlying mechanistic basis of regional-dependent intestinal drug absorption, which has led to many attempts to deliver drugs to specific regions throughout the GIT, aiming to optimize drug absorption, bioavailability, pharmacokinetics, and/or pharmacodynamics. In the book "Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation" we aim to highlight the current progress and to provide an overview of the latest developments in the field of regional-dependent intestinal drug absorption and delivery, as well as pointing out the unmet needs of the field.
    Keywords: bioequivalence ; Biopharmaceutics Classification System ; in vitro ; dissolution test ; pravastatin ; oral absorption ; in silico modeling ; GastroPlus ; Phoenix WinNonlin ; pharmacokinetics ; clinical studies ; ibuprofen ; manometry ; gastrointestinal ; mechanistic modeling ; PBPK ; PBBM ; disintegration ; dissolution ; enteric-coated ; ICH ; quality control ; regional intestinal permeability ; permeation enhancers ; absorption-modifying excipients ; oral peptide delivery ; intestinal perfusion ; pharmaceutical development ; controlled release drug product ; biopharmaceutics classification system ; drug solubility ; drug permeability ; location-dependent absorption ; segregated flow intestinal model (SFM) ; traditional model (TM) ; route-dependent intestinal metabolism ; first-pass effect ; drug-drug interactions ; DDI ; in vitro in vivo extrapolations ; IVIVE ; zero-order absorption ; first-order absorption ; combined zero- and first-order absorption ; transit compartment absorption model ; in situ perfusion ; microdevices ; shape ; mucoadhesion ; colon absorption ; nutrient digestion ; nutrient absorption ; gastrointestinal hormone ; postprandial glycaemia ; energy intake ; region of the gut ; obesity ; type 2 diabetes ; Franz–PAMPA ; BCS drugs ; biomimetic membrane ; Franz cell ; passive drug transport ; BCS class IV drugs ; segmental-dependent intestinal permeability ; intestinal absorption ; oral drug delivery ; biopharmaceutics ; physiologically-based pharmacokinetic (PBPK) modeling ; furosemide ; intestinal permeability ; human colon carcinoma cell layer (Caco-2) ; hierarchical support vector regression (HSVR) ; drug absorption ; drug solubility/dissolution ; regional/segmental-dependent permeability and absorption ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KND Manufacturing industries::KNDP Pharmaceutical industries
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  • 6
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    Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2022-03-21
    Description: This book is a compendium of scientific articles submitted to a Special Issue of International Journal of Molecular Sciences, fostered by MDPI and curated by Dr. Annamaria Sandomenico and Dr. Menotti Ruvo from the Institute of Biostructure and Bioimaging of the National Research Council. All articles underwent a rigorous peer review and were selected to highlight the properties that make monoclonal antibodies and their functional fragments some of the most useful and versatile assets in therapy and diagnosis.
    Keywords: porcine deltacoronavirus ; nucleocapsid ; monoclonal antibodies ; neurodegenerative disorders ; affibody molecules ; blood–brain barrier ; receptor-mediated transcytosis ; transferrin receptor ; AL amyloidosis ; CD38 ; anti-CD38 MoAb ; Daratumumab ; Isatuximab ; myeloma ; BCMA ; bispecific T-cell engager ; antibody-drug conjugates ; chimeric antigen receptor T-cells ; belantamab mafodotin ; idecabtagene vicleucel ; JNJ-68284528 ; Mabs ; Antibody-Drug Conjugate ; cancer therapy ; drug targeting ; payload ; cross-linking ; antibody fragment ; Fab ; scFv ; E. coli ; YKL-40 ; CHI3L1 ; monoclonal antibody ; phage display ; lung metastasis ; prostate-specific membrane antigen ; in vivo imaging ; prostate cancer ; glutamate carboxypeptidase II ; NAALADase ; immunization ; antibody ; protocol ; guinea pig ; cDNA ; chimeric antigen receptor (CAR T) ; universal CAR T ; modular CAR T ; universal immune receptor ; CAR adaptor ; adoptive immunotherapy ; split CAR ; bispecific ; polyspecificity ; pharmacokinetics ; solubility ; aggregation ; viscosity ; developability ; stability ; affinity ; specificity ; protein engineering ; self-association ; non-specific binding ; immunogenicity ; antibody fragments ; single chain ; amyloid ; oligomer ; neurotoxicity ; NUsc1 ; bic Book Industry Communication::T Technology, engineering, agriculture::TB Technology: general issues
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  • 7
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    Derivatization in Analytical Chemistry (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2022-06-21
    Description: Derivatization is one of the most widely used sample pretreatment techniques in Analytical Chemistry and Chemical Analysis. Reagent-based or reagent-less schemes offer improved detectability of target compounds, modification of the chromatographic properties and/or the stabilization of sensitive compounds until analysis. Either coupled with separation techniques or as a “stand alone” analytical procedure, derivatization offers endless possibilities in all aspects of analytical applications.
    Keywords: tyrosine kinase inhibitors ; chloranilic acid ; charge-transfer reaction ; 96-microwell spectrophotometric assay ; high-throughput pharmaceutical analysis ; biogenic amines ; Lycium barbarum L. ; HPLC ; derivatization ; amino acids ; esterification ; GC–MS ; pentafluoropropionic anhydride ; stability ; toluene ; pigment ; linseed oil ; derivatisation ; quantification ; P/S ratio ; A/P ratio ; ∑D ; GC-MS ; ureide ; BSTFA ; creatine ; creatinine ; silylation ; TMS ; validation ; low-molecular-weight thiols ; human serum albumin ; α-lipoic acid ; blood plasma ; monobromobimane ; reduction ; sodium borohydride ; high-performance liquid chromatography ; fluorescence detection ; taurine ; glutamine ; clams ; high-resolution mass spectrometry ; nerve agents ; methylation ; chemical warfare agents ; sarin ; Novichoks ; 2-naphthalenethiol ; sulforaphane ; HPLC-UV/Vis ; pharmacokinetics ; acetonitrile-related adducts ; acetylenic lipids ; double and triple bond localization ; in-source derivatization ; mass spectrometry ; acetazolamide ; carbonic anhydrase ; enhancement ; inhibition ; pentafluorobenzyl bromide ; chiral metabolomics ; rice water ; d-amino acids ; enantiomer separation ; dimethyl labeling ; homocysteine thiolactone ; homocysteine ; zone fluidics ; o-phthalaldehyde ; fluorosurfactant-modified gold nanoparticles ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PN Chemistry ; bic Book Industry Communication::P Mathematics & science::PN Chemistry::PNF Analytical chemistry
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  • 8
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    Coffee and Caffeine Consumption for Human Health (2021)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2024-04-05
    Description: The year 2019 has been prolific in terms of new evidence regarding the effects of coffee and caffeine consumption on diverse aspects of human functioning. This book collects 20 high-quality manuscripts published in Nutrients that include original investigation or systematic review studies of the effects of caffeine intake on human performance and health. The diversity of the articles published in this Special Issue highlights the extent of the effects of coffee and caffeine on human functioning, while underpinning the positive nature of most of these effects. This book will help with understanding why the natural sources of caffeine are so widely present in the nutrition behaviors of modern society.
    Keywords: QH301-705.5 ; Q1-390 ; TX341-641 ; NAT ; n/a ; supplementation ; EEG–EMG coherence ; muscle function ; tea ; fatigue ; ergogenic ; adrenal gland ; skeletal muscle ; xanthine oxidase ; placebo ; CMJ ; efficiency ; colorectal cancer ; rat ; pregnancy ; coffee/caffeine ; Wingate ; 1RM test ; supplement ; actigraphy ; athletic ; systematic review and meta-analysis ; women ; consumption motives ; resistance training ; cancer prevention ; sport supplement ; exercise ; DOMS ; placebo effect ; sprint performance ; power ; behavior ; belief ; health ; perceptions ; exercise performance ; ergogenic aid ; electromyography ; ergogenic effect ; corticosterone ; metabolome ; mood state ; muscle contraction ; strength ; energy drink ; repetition ; responders ; perception ; anaerobic ; CYP450 ; puberty ; energy drinks ; isokinetic testing ; individual responses ; phenotyping ; nutrition ; time under tension ; menstrual cycle ; exercise training ; RPE ; ergogenic substances ; upper limb ; elite athlete ; recovery ; speed ; epidemiology ; caffeine ; sex-difference ; bench press ; pharmacokinetics ; sport performance ; ergogenic aids ; expectancy ; consumer ; football ; newborn ; velocity ; metabolites ; performance ; coffee ; prospective studies ; resistance exercise ; sport ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
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  • 9
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    Amide Bond Activation (2021)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2024-04-05
    Description: The amide bond represents a privileged motif in chemistry. The recent years have witnessed an explosion of interest in the development of new chemical transformations of amides. These developments cover an impressive range of catalytic N–C bond activation in electrophilic, Lewis acid, radical, and nucleophilic reaction pathways, among other transformations. Equally relevant are structural and theoretical studies that provide the basis for chemoselective manipulation of amidic resonance. This monograph on amide bonds offers a broad survey of recent advances in activation of amides and addresses various approaches in the field.
    Keywords: QD1-999 ; Q1-390 ; QD450-801 ; N-heterocyclic carbene ; non planar amide ; ruthenium (Ru) ; physical organic chemistry ; gemcitabine prodrug ; pyramidal amides ; bridged sultams ; catalysis ; dipeptides ; N-(1-naphthyl)acetamide ; C-N ? bond cleavage ; steric effects ; peptide bond cleavage ; transition-metal-free ; palladium ; N-heterocyclic carbenes (NHCs) ; addition reaction ; C–O activation ; rhodium ; metal complexes ; carbanions ; thioamidation ; amide bond ; intramolecular catalysis ; antiviral activity ; additivity principle ; pre-catalysts ; C–N bond cleavage ; bridged lactams ; C–H acidity ; arynes ; twisted amides ; organic synthesis ; amination ; Suzuki-Miyaura ; tert-butyl ; cyclopentadienyl complexes ; C-S formation ; enzymes ; DFT study ; sulfonamide bond ; N ; HERON reaction ; primaquine ; entropy ; amide activation ; amidation ; synthesis ; amide hydrolysis ; carbonylicity ; amide bond activation ; amide bond resonance ; aminosulfonylation ; molecular dynamics ; model compound ; in situ ; amide ; homogeneous catalysis ; heterocycles ; anomeric effect ; multi-component coupling reaction ; kinetic ; excited state ; C–H bond cleavage ; palladium catalysis ; amides ; thiourea ; formylation ; alkynes ; cis/trans isomerization ; amide C–N bond activation ; intein ; C-H functionalization ; succindiamide ; amide bonds ; crown ether ; aminoacylation ; directing groups ; cytostatic activity ; reaction thermodynamics ; acyl transfer ; transition metals ; N-dimethylformamide ; DMAc ; acylative cross-coupling ; C-H/C-N activation ; nickel catalysis ; antibacterial screening ; sodium ; aryl thioamides ; Winkler-Dunitz parameters ; catalyst ; N-dimethylacetamide ; base-catalyed hydrolysis ; nitrogen heterocycles ; cross-coupling ; insertion ; amidicity ; nitro-aci tautomerism ; activation ; carbonylation ; transamidation ; amine ; distortion ; Pd-catalysis ; rotational barrier energy ; hypersensitivity ; N–C activation ; metabolic stability ; [2+2+2] annulation ; twisted amide ; protease ; cyanation ; amide resonance ; trialkylborane ; catalysts ; biofilm eradication ; pharmacokinetics ; pancreatic cancer cells ; DMF ; aryl esters ; Michael acceptor ; fumardiamide ; water solvation ; ester bond activation ; cyclization ; nuclear magnetic resonance ; secondary amides ; reaction mechanism ; density functional theory ; density-functional theory ; amino acid transporters ; thema EDItEUR::P Mathematics and Science::PN Chemistry
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  • 10
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    Recent Trends in Pharmaceutical Analytical Chemistry (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2024-03-27
    Description: This book covers the most recent research trends and applications of Pharmaceutical Analytical Chemistry. The included topics range from the adulteration of dietary supplements, to the determination of drugs in biological samples with the aim to investigate their pharmacokinetic properties.
    Keywords: growth hormone ; long-acting Fc-fusion recombinant human growth hormone ; method validation ; cell-based bioassay ; reporter gene assay ; pharmacokinetics ; tissue distribution ; alnustone ; rats ; LC-MS/MS ; inflammatory bowel disease ; fixed-dose combination ; biomimetic chromatography ; thiopurine immunosuppressants ; folic acid ; doxorubicin ; hernandezine ; pharmacokinetic study ; drug–drug interaction ; gardneramine ; monoterpenoid indole alkaloid ; memantine ; rimantadine ; amantadine ; zone fluidics ; o-phthalaldehyde ; derivatization ; stopped-flow ; quality control ; anwuligan ; rat ; optode ; polyhexamethylene biguanide hydrochloride ; lactone-rhodamine B ; contact-lens detergent ; dietary supplement ; adulteration ; low-field NMR ; multivariate analysis ; steroids ; Partial Least Squares regression ; in vitro permeability ; predictive model ; ketamine ; norketamine ; high throughput bar adsorptive microextraction ; LVI-GC-MS(SIM) ; urine ; baricitinib ; UPLC-MS/MS ; irbersartan ; n/a ; thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general
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  • 11
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    Drug Metabolism, Pharmacokinetics and Bioanalysis (2021)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2023-12-21
    Description: Drug metabolism/pharmacokinetics and drug interaction studies have been extensively carried out in order to secure the druggability and safety of new chemical entities throughout the development of new drugs. Recently, drug metabolism and transport by phase II drug metabolizing enzymes and drug transporters, respectively, as well as phase I drug metabolizing enzymes, have been studied. A combination of biochemical advances in the function and regulation of drug metabolizing enzymes and automated analytical technologies are revolutionizing drug metabolism research. There are also potential drug–drug interactions with co-administered drugs due to inhibition and/or induction of drug metabolic enzymes and drug transporters. In addition, drug interaction studies have been actively performed to develop substrate cocktails that do not interfere with each other and a simultaneous analytical method of substrate drugs and their metabolites using a tandem mass spectrometer. This Special Issue has the aim of highlighting current progress in drug metabolism/pharmacokinetics, drug interactions, and bioanalysis.
    Keywords: R5-920 ; RM1-950 ; human liver microsomes ; alcohol addiction ; UGT ; ultra-high-pressure liquid chromatography ; adalimumab ; procainamide ; LC-MS/MS ; DA-9805 ; paeonol ; LC-QTOF-MS/MS ; YRA-1909 ; chlorogenic acid ; immunoprecipitation ; Eurycoma longifolia ; CYP ; caffeic acid ; rat ; pharmaceutical excipient ; Korean red ginseng extract ; Stauntonia hexaphylla leaf extract ; bioanalysis ; HPLC-MS/MS ; B6 ; eurycomanone ; bioavailability ; drying technology ; GB3 ; diclofenac ; 129-Glatm1Kul/J ; aglycone ; caffeic acid O-glucuronides ; organic anion transporting polypeptide ; protein precipitation ; metabolic stability ; Fabry disease ; biopharmaceuticals ; imperatorin ; neochlorogenic acid ; gastric ulcer ; saikosaponin a ; hair ; anthraquinone ; acetyl tributyl citrate ; pharmacokinetics ; brain distribution ; mematine ; ethyl glucuronide ; pharmacokinetic ; loxoprofen ; liquid chromatography-quadrupole TOF MS ; glucuronidation ; esomeprazole ; metformin ; cytochrome P450 ; glycoside ; AUDIT score ; protein stability ; efficacy ; LC-HR/MS ; cryptochlorogenic acid ; aceclofenac ; drug interaction ; liquid chromatography-tandem mass spectrometry ; Osthenol ; plasma ; N-acetylprocainamide ; diabetes ; bic Book Industry Communication::M Medicine
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    In Vivo Nuclear Molecular Imaging in Drug Development and Pharmacological Research (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2024-03-28
    Description: This Special Issue published one editorial, eight articles and four reviews from approximately one hundred authors. It aimed to provide cutting-edge research on pre-clinical development and the clinical translation of radiopharmaceuticals within the molecular imaging community. The Special Issue covered radioligand development, existing radiotracer optimization, imaging agent evaluation in animal models, the clinical production of radiopharmaceuticals, and investigative research on the use of molecular imaging probes in human subjects. We appreciate all the authors’ significant contributions to this Special Issue and hope the readers will enjoy the content.
    Keywords: nanoparticle ; multimodal imaging ; photoacoustic ; heterobivalent peptide ; Alzheimer’s disease ; amyloid-beta ; animal model ; astrocyte ; blood–brain barrier ; imaging ; metabolism ; microglia ; neuroinflammation ; neurotransmitter receptors ; positron emission tomography ; synaptic density ; vascular imaging ; FDG ; PET/CT ; microvasculature imaging ; ABC-transporter ; drug-induced liver injury ; hepatotoxicity ; organic anion-transporting polypeptide ; pharmacokinetics ; liver function ; SLC-transporter ; V/Q PET/CT ; [68Ga]Ga-MAA ; 68Ga-labelled carbon nanoparticles ; glioblastoma ; fluorescence guided surgery ; 5-ALA ; fluorescein ; NIR-AZA ; magnetic resonance imaging ; high resolution ; hybrid imaging ; psychiatric disorders ; extracellular vesicles (EVs) ; umbilical cord mesenchymal stem cell (UCMSC) ; diabetes ; I-124 ; positron emission tomography (PET) ; intravenous (I.V.) administration ; intra-arterial (I.A.) administration ; biodistribution ; fluorine-18 ; PET ; oxime ; PSMA ; lipophilicity ; radiometals ; copper-61 ; liquid targets ; post-processing ; [61Cu]Cu-DOTA-NOC ; [61Cu]Cu-DOTA-TOC ; [61Cu]Cu-DOTA-TATE ; FAP ; 99mTc-FAP inhibitor ; 99mTc-labeled iFAP ; tumor microenvironment ; SPECT ; GluN1/2B receptors ; NMDA ; [3H]ifenprodil ; σ1 and σ2 receptors ; receptor occupancy ; PET imaging ; drug development ; neurodegenerative diseases ; n/a ; thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
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    Method Development and Validation in Food and Pharmaceutical Analysis (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2023-02-02
    Description: This reprint covers a wide range of topics including, but not limited to, new analytical and bioanalytical methods relevant to the separation, identification, and determination of substances in pharmaceutics, pharmacokinetics, nanobiotechnology, clinical chemistry, and related disciplines; methods for the identification of bioactive compounds in functional foods and medicinal plants; applications of chromatography and allied techniques in biomedical sciences.
    Keywords: wild rice ; antioxidant ; macroporous resins ; LC-MS/MS ; phenolics ; procyanidins ; osimertinib ; UPLC-TOF-MS ; rat ; pharmacokinetics ; carbonyl derivatization ; phenylhydrazine ; phenylenediamine ; hydroxylamine ; water analysis ; lipoxidation ; lisdexamfetamine dimesylate ; impurities ; structural elucidation ; forced degradation ; HPLC validation ; chemical constituent profiles of Sinisan ; chinese medicine processing ; chinese medicinal formula compatibility ; Dendropanax morbifera leaf ; xanthine oxidase ; hyperuricemia ; HPLC ; advanced glycation end-products (AGEs) ; Nε-(carboxymethyl) lysine (CML) ; Nε-(carboxyethyl) lysine (CEL) ; antler velvet processing ; UPLC-MS/MS ; Cinnamomum yabunikkei leaf ; elastase ; Citrus junos Seib ex TANAKA ; rhKGF-1 ; rhKGF-2 ; bioactivity ; cell-based bioassay ; method validation ; CYP450 enzyme ; cocktail probe drug ; RT-PCR ; galangin ; affecting factors ; amadori compound ; furosine ; Maillard reaction ; velvet antler processing ; Brazilian green propolis ; phenolic acids ; UPLC-ESI-QTOF-MS ; quantitation ; methodological verification ; Glycyrrhizae Radix extract ; glycyrrhizin ; isoliquiritigenin ; liquiritigenin ; liquiritin ; LC–MS/MS analysis ; desoxo-narchinol A ; Nardostachys jatamansi ; bioavailability ; silybin ; silymarin product ; comparative pharmacokinetics ; ginsenosides ; red ginseng extract ; human ; acanthus ilicifolius herb ; phenylethanoid glycosides ; C.tricuspidata Bureau ; tyrosinase ; dialyzable leukocyte extract ; Transferon® ; complex mixture of peptides ; quality specifications ; biological potency ; development and validation ; Dioscorea nipponica Makino ; steroidal saponin ; HPLC-UV ; UPLC-QTOF/MS ; validation ; osteosarcoma ; apoptosis ; epinastine ; comparison ; SH-1242 ; 2-(3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-6-yl)ethanone ; HPLC-MS/MS ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PN Chemistry ; bic Book Industry Communication::P Mathematics & science::PN Chemistry::PNF Analytical chemistry
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    Drug Metabolism/Transport and Pharmacokinetics (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2024-03-31
    Description: This book serves to highlight the pharmacokinetics/drug–drug interactions and mechanistic understanding in relation to the drug-metabolizing enzymes and drug transporters.This book presents a series of drug metabolism and transport mechanisms that govern the pharmacokinetic features of therapeutic drugs as well as natural herbal medicines. It also covers the pharmacokinetic interactions caused by inhibiting or inducing the metabolic or transport activities under disease states or the coadministration of potential inhibitors. It also deals with microenvironmental pharmacokinetic profiles as well as population pharmacokinetics, which gives new insights regarding the pharmacokinetic features with regard to drug metabolism and transporters.
    Keywords: tofacitinib ; dose-dependent pharmacokinetics ; hepatic and intestinal first-pass effect ; rats ; catalposide ; in vitro human metabolism ; UDP-glucuronosyltransferase ; sulfotransferase ; carboxylesterase ; celecoxib ; drug–drug interaction ; fluorescence ; HPLC ; metabolism ; repaglinide ; HSG4112 ; anti-obesity agent ; stereoselectivity ; pharmacokinetics ; compound K ; protopanaxadiol (PPD) ; biliary excretion ; intestinal metabolism ; Carthamus tinctorius extract ; notoginseng total saponins ; comparative pharmacokinetic study ; large volume direct injection ; compatibility mechanism ; mertansine ; human hepatocytes ; cytochrome P450 ; UDP-glucuronosyltransferases ; sodium-glucose cotransporter 2 (SGLT2) inhibitors ; DWP16001 ; kidney distribution ; inhibition mode ; diabetes ; transporter-enzyme interplay ; influx transporter ; efflux transporter ; physiologically based pharmacokinetic model ; cytochrome P450 enzymes ; tiropramide ; healthy Korean subjects ; modeling ; population pharmacokinetic ; quercetin ; breast cancer resistance protein ; inhibitor ; prazosin ; sulfasalazine ; kinetic analysis ; food–drug interactions ; Caco-2 ; EpiIntestinal ; first-pass ; P-gp ; BCRP ; drug transporter ; CYP3A4 ; oral availability ; automatization ; drug absorption ; drug dosing ; head-and-neck cancer ; real-time measurements ; taxanes ; tissue engineering ; UHPLC-MS/MS ; metformin ; verapamil ; drug interaction ; organic cation transporter 2 ; renal excretion ; acute renal failure ; gentamicin ; cisplatin ; hepatic CYP3A1(23) ; creatinine clearance ; renal clearance ; nonrenal clearance ; thema EDItEUR::M Medicine and Nursing ; thema EDItEUR::K Economics, Finance, Business and Management::KN Industry and industrial studies::KND Manufacturing industries
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    Advances in Production, Properties and Applications of Sprouted Seeds (2021)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2024-03-27
    Description: Sprouted grains are food ingredients widely appreciated for their improved nutritional, functional, organoleptic, and textural properties compared with non-germinated grains. In recent years, sprouting has been explored as a promising green food engineering strategy to improve the nutritional value of grains and the formation of secondary metabolites with potential application in the functional food, nutraceutical, pharmaceutical, and cosmetic markets. However, little attention has been paid to the impact of sprouting on the chemical composition, safety aspects, and technofunctional and chemopreventive properties of sprouted seeds and their derived flours and byproducts. The six articles included in this Special Issue present insightful findings on the most recent advances regarding new applications of sprouted seeds or products derived thereof, evaluations of the nutritional value and phytochemical composition of sprouts during production or storage, and explorations of their microbiological, bioactive, and technofunctional properties.
    Keywords: biochemical characteristic ; enzymatic browning ; inhibitory profile ; lentil ; sprouts ; polyphenol oxidase ; purification ; germinated oat ; avenanthramides ; colorectal cancer ; chemoprevention ; bran ; cell walls ; sprouting ; dough rheology ; bread-making ; microstructure ; barley ; germination ; flour ; RSM ; nutritional properties ; bioactive compounds ; quality ; melatonin ; bioavailability ; lentil sprouts ; phenolic compounds ; antioxidant status ; pharmacokinetics ; food safety ; legumes ; microbial contamination ; protein ; mineral ; seed germination ; nutritional value ; phytochemicals ; bioactivity ; health ; technological properties ; food development ; functional foods ; thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general
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    Antimicrobial Therapy in Intensive Care Unit (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2023-04-05
    Description: This reprint is an excellent collection of articles that deal with difficult-to-treat infections in the ICU environment. Multiresistant bacteria and fungi create severe treatment problems to the physician charged with their care. We hope that this book will help everyday dilemmas and add useful information on difficult topics.
    Keywords: Acinetobacter ; pandrug-resistant ; antimicrobial combinations ; synergy ; renal replacement therapy ; Monte Carlo simulation ; antibiotics ; pharmacokinetics ; pharmacodynamics ; microbiome ; probiotics ; intensive care unit ; dysbiosis ; ventilator-associated pneumonia ; extracorporeal membrane oxygenation ; ECMO ; critical illness ; antibiotic choices ; HAP ; VAP ; colonization ; antibiotic pressure ; bloodstream infection ; bacteraemia ; sepsis ; septic shock ; empirical ; probabilistic antibiotics ; source control ; de-escalation ; ICU ; intensive care ; antimicrobial stewardship ; COVID-19 ; procalcitonin ; C-reactive protein ; presepsin ; infection ; biomarker ; guided antimicrobial therapy ; APACHE II score ; bacteremia ; broth microdilution ; colistin ; colistin-resistant ; Gram-negative ; mortality ; SOFA score ; candidemia ; incidence ; epidemiology ; Candida species ; non-albicans Candida species ; fluconazole resistance ; critically ill ; beta-lactam antibiotics ; Acinetobacter baumannii ; antibiotic optimisation ; antibiotic stewardship (AMS) ; aspiration pneumonia ; hospital-acquired pneumonia (HAP) ; multidrug-resistance (MDR) ; non-fermentative Gram-negative bacilli (GNB) ; polymicrobial ; pneumonia resolution ; ventilator-associated pneumonia (VAP) ; carbapenem-resistant A. baumannii (CRAb) ; infection control ; antimicrobial agents ; carbapenems ; antibiotic resistance ; clinical pharmacy services ; Klebsiella pneumoniae ; Pseudomonas aeruginosa ; salvage treatment ; double carbapenem ; newer β-lactam-β-lactamase inhibitors ; cefiderocol ; eravacycline ; SARS-CoV-2 infection ; mechanical ventilation ; risk factors ; blood stream infection ; defined daily dose ; antibiotics utilization ; empiric ; n/a ; bic Book Industry Communication::M Medicine
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    Therapeutic Monoclonal Antibodies and Antibody Products, Their Optimization and Drug Design in Cancers (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2022-02-24
    Description: The book broadly deals with therapeutic monoclonal antibodies (mAbs) and various relevant topics, including different antibody formats such as Antibody–Drug Conjugates (ADC), bispecifics, nanoparticle-based mAbs and HER2+ cancers, immune checkpoint inhibitors and other closely related topics. Each paper was written by leading active research groups in their fields both from academia and industry. The book should be of interest to those scientists and researchers who develop or use biologics, biotherapeutics, biosimilars and biobetters in cancer treatment.
    Keywords: monoclonal antibody ; NSCLC ; immunotherapy ; ELISA ; pharmacokinetics ; pharmacogenetics ; anti-PD-1 monoclonal antibodies ; anti-acetylcholine receptor (AChR) antibody ; B cell ; immune checkpoint blockade ; immune-related adverse events (irAEs) ; myasthenia gravis (MG) ; non-small-cell lung cancer (NSCLC) ; nivolumab ; programmed cell death ligand 1 (PD-L1) ; T cell ; tetraspanins ; cancer ; Tspan8 ; radioimmunotherapy ; immune-checkpoint inhibitors ; LDH ; biomarkers ; Ang-2 ; antiangiogenic therapy ; in vivo imaging ; radio- and chemotherapy ; VEGF-A ; cancer therapy ; neovascularization ; angiogenesis ; tumor microenvironment ; colorectal cancer ; antibody ; NK cells ; ADCC ; CD133 ; prominin-1 ; gold nanoparticles ; antibody-drug conjugates ; cell penetrating peptide ; HIV-1 TAT ; active-targeting ; targeted delivery ; trastuzumab ; MMAE ; valine-citrulline ; affibody ; drug conjugates ; hepatic uptake ; DM1 ; dermatooncology ; immune checkpoints ; monoclonal antibodies ; passive immunotherapy ; canine B-cell lymphoma ; DLA-DR ; HLA-DR ; antibody-drug conjugate ; ADC ; methotrexate ; tumor immunity ; combination therapy ; multiple myeloma (MM) ; monoclonal antibodies (mAbs) ; antibody products ; B cell maturation antigens (BCMAs) ; bispecific T cell engagers (BiTEs®) ; checkpoint inhibitors 1 ; protein structure 2 ; pharmacokinetics 3 ; drug optimization 4 ; HER2-positive breast cancer ; metastatic disease ; neoadjuvant and adjuvant therapy ; targeted therapy ; acute myeloid leukemia ; CD123 ; IL3RA ; kinesin spindle protein inhibitor ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KND Manufacturing industries::KNDP Pharmaceutical industries
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    Coffee and Caffeine Consumption for Human Health (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2022-11-17
    Description: Caffeine is present in coffee and many other beverages and is the most widely used central nervous system stimulant. Coffee drinking or caffeine supplementation may have a role in preventing cardiometabolic and endocrine disease, neuroinflammation, cancer, and even all-cause mortality. Other aspects are either less known or controversial, including the effects on the brain–gut axis, neurodevelopment, behavior, pain, muscle–skeletal health, skin or sexual function. Studies focusing on special populations (neonates, children, adolescents, athletes, elderly, pregnant and nonpregnant women), or interactions with other drugs and foods, are relatively scarce but of obvious interest. Other compounds present in coffee and other caffeinated food stuffs may affect caffeine´s physiological effects with a tremendous impact on health. This Special Issue, which contains twenty-one manuscripts, has focused on some of these varied topics, providing further evidence of the multiple health benefits that coffee/caffeine intake may exert in humans, at least in specific populations (with a particular genetic profile or suffering from specific diseases). However, the specific effects in the different organs and systems, as well as the mechanisms involved are not yet clear. Furthermore, within the current context aiming to sustainable development, the coffee plant Coffee sp. and its so-far relatively neglected by-products are expected to become soon a source of ingredients for new functional foods whose properties will need to be precisely determined. We hope the readers of this Special Issue will find inspiration for new studies on the topic.
    Keywords: pharmacokinetics ; energy drink ; exercise ; elite athlete ; performance ; football ; RPE ; DOMS ; sport performance ; supplementation ; ergogenic aids ; consumer ; behavior ; perception ; coffee ; health ; consumption motives ; coffee/caffeine ; systematic review and meta-analysis ; prospective studies ; epidemiology ; cancer prevention ; colorectal cancer ; individual responses ; responders ; exercise performance ; caffeine ; tea ; energy drinks ; pregnancy ; newborn ; ergogenic aid ; resistance training ; isokinetic testing ; adrenal gland ; corticosterone ; puberty ; rat ; sex-difference ; fatigue ; mood state ; supplement ; resistance exercise ; speed ; repetition ; n/a ; metabolome ; skeletal muscle ; muscle contraction ; ergogenic effect ; bench press ; upper limb ; ergogenic substances ; time under tension ; 1RM test ; metabolites ; phenotyping ; CYP450 ; NAT ; xanthine oxidase ; actigraphy ; athletic ; anaerobic ; CMJ ; nutrition ; sport supplement ; Wingate ; electromyography ; efficiency ; sport ; expectancy ; belief ; perceptions ; placebo effect ; recovery ; strength ; power ; sprint performance ; menstrual cycle ; placebo ; ergogenic ; EEG–EMG coherence ; women ; exercise training ; velocity ; muscle function ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences ; bic Book Industry Communication::J Society & social sciences::JF Society & culture: general::JFC Cultural studies::JFCV Food & society
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    Monoclonal Antibody-Directed Therapy (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2022-02-24
    Description: The book deals with therapeutic monoclonal antibodies (mAbs) broadly, and relevant topics such as challenges and opportunities, next-generation antibody products, Antibody-Drug-Conjugates (ADC), bispecifics, glycosylation, and T-cell engagers are covered. Each topic has been written by leading groups around the world and the book should be of interest to researchers from both academia and industry.
    Keywords: therapeutic antibody ; stability ; aggregation ; manufacture challenges ; formulation ; antibodies ; site-specific conjugation ; bioconjugates ; ADC ; antibody-drug conjugates ; payloads ; linkers ; nucleic acids ; ADME ; developability ; glycosylation ; post-translational modifications ; pharmacokinetics ; effector functions ; antibody-dependent cell-mediated cytotoxicity ; complement-dependent cytotoxicity ; immunogenicity ; pharmacodynamics ; glycoengineering ; type III secretion system ; prophylaxis ; antibacterials ; antibiotics ; HIV/AIDS ; co-formulation ; high concentration ; analytical characterization ; antibody (s) ; T-cell engagers ; bispecific antibodies ; immunotherapy ; oncology ; antibody engineering ; immunological synapse ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KND Manufacturing industries::KNDP Pharmaceutical industries
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    Polymers Enhancing Bioavailability in Drug Delivery, 2nd Edition (2024)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2024-01-08
    Description: This Special Issue provides an update on the state of the art and current trends in polymeric drug delivery systems specifically designed for improving drug bioavailability. The multiple contributions received further strengthen the role of polymers in modern drug delivery and targeting, illustrating the different approaches possible and unveiling what the future may bring.
    Keywords: Histoplasma capsulatum ; PLGA ; Itraconazole ; macrophage ; functionalized nanoparticle ; F4/80 receptor ; rutin ; nanocrystals ; anti-inflammatory ; hydroxypropyl beta-cyclodextrin ; nanoparticles ; budesonide ; chitosan ; colon delivery ; eudragit ; pellets ; ferrisilicate ; PEG ; insulin ; encapsulation ; diabetic mellitus ; polypeptides ; drug delivery ; doxorubicin ; cancer ; topology of poly-l-cystein ; antimicrobial ; antifouling ; pH sensitivity ; zwitterionic polymers ; gamma radiation ; copolyester ; SPION ; cysteine ; bioconjugation ; and enzymatic release ; polymeric nanoparticles ; drug delivery and targeting ; ocular posterior segment ; oxidative stress ; retinal degeneration ; nerve growth factor ; peanut agglutinin ; zebrafish ; molecular dynamics simulation ; interaction energy ; hydrogen bonding ; solid dispersion ; hot melt extrusion ; amorphous formulation ; tacrolimus ; sucrose acetate isobutyrate ; amorphous solid dispersion ; dissolution ; stability ; pharmacokinetics ; phytomedicine ; nanosponges ; lactoferrin ; bioavailability ; MDA-MB-231 cells ; caspase-3 ; cyclin-D1 ; dendrimers ; Janus nanoparticles ; biocompatibility ; nanoformulation ; pharmaceuticals ; 3D printing ; hybrid scaffold ; polycaprolactone ; vancomycin ; mesenchymal stem cells ; tissue engineering ; drug delivery systems (DDSs) ; osteomyelitis ; n/a ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences::PSB Biochemistry
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    Advanced Blood-Brain Barrier Drug Delivery (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2023-02-02
    Description: Advanced Blood-Brain Barrier Drug Delivery is a reprint with a summary editorial, followed by 16 chapters that cover five areas of brain drug delivery, including receptor-mediated transport (RMT), carrier-mediated transport (CMT), active efflux transport (AET), Trojan horse lipid nanoparticles (LNP), and in vivo methods for measurement of drug transport across the blood–brain barrier (BBB).
    Keywords: blood–brain barrier (BBB) ; brain drug delivery ; prodrugs ; solute carriers (SLCs) ; lysosomal storage disease ; neuronopathic mucopolysaccharidosis ; blood–brain barrier ; neurodegeneration ; enzyme replacement therapy ; receptor-mediated transcytosis ; transferrin receptor ; insulin receptor ; endothelium ; receptor-mediated transport ; carrier-mediated transport ; genetic engineering ; IgG fusion proteins ; nanoparticles ; liposomes ; TrkB ; agonist antibody ; variable new antigen receptor (VNAR) ; neuroprotection ; transferrin receptor 1 (TfR1) ; blood-brain barrier (BBB) ; 6-OHDA ; Parkinson’s disease ; bispecific antibody ; alpha-synuclein (αSYN) ; Parkinson’s disease (PD) ; immunotherapy ; monoclonal antibody ; transferrin receptor (TfR) ; receptor-mediated transcytosis (RMT) ; single domains antibody ; IGF1R ; neurotensin ; protein-based therapy ; lysosomal storage disorders ; fusion proteins ; Alzheimer’s disease ; neurotrophic factors ; decoy receptors ; ATP-binding cassette transporters ; drug delivery ; ischemic stroke ; SLC transporters ; lipid nanoparticle ; ssPalm ; mRNA transfection ; hCMEC/D3 cells ; cell toxicity ; SWATH-MS ; translation ; chaperonin-containing TCP-1 ; proton-coupled organic cation antiporter ; photo-affinity labeling ; proteomics ; SWATH-MS (sequential window acquisition of all theoretical-mass spectra) ; pharmacokinetics ; compartmental models ; physiologically based PK models ; blood-brain barrier ; antibody ; cavernous sinus ; BBB–peptide shuttle ; brain delivery ; solute carrier (SLC) transporters ; amyotrophic lateral sclerosis (ALS) ; NSC-34 cell lines ; taurine transporter (Taut) ; large amino acid transporter 1 (LAT1) ; monocarboxylate transporters (MCTs) ; organic cation transporters (OCTNs) ; choline transporter-like protein-1 (CTL1) ; TNF-α inhibitor ; molecular Trojan horse ; endosomal ; liposome ; nanoparticle ; targeting ; transferrin ; n/a ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MM Other branches of medicine::MMG Pharmacology
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    Precision Medicine (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2022-08-12
    Description: This colligated Special Issue of Pharmaceutics on Precision Medicine: Applied Concepts of Pharmacogenomics in Patients with Various Diseases and Polypharmacy offers to the reader a series of articles that describe the concept of Precision Medicine, discuss its implementation process and limitations, demonstrate its value by illustrating some clinical cases, and open the door to new and more sophisticated techniques and applications.
    Keywords: fibromyalgia (FM) ; myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) ; microRNA ; miRNome ; pharmacogenomics ; pharmacoepigenomics ; SM2miR ; Pharmaco-miR ; repoDB ; ME/CFS Common Data Elements (CDEs) ; dihydropyrimidine dehydrogenase ; DPYD ; 5-fluorouracil ; fluoropyrimidine ; therapeutic drug monitoring ; orthotopic liver transplant ; busulfan ; glutathione S-transferase ; genetic polymorphism ; limited sampling strategy ; pharmacokinetics ; clinical pharmacogenetics ; pharmacogenetic testing ; adverse drug reactions ; genotype ; phenotype ; pharmacogene ; barriers to pharmacogenetics implementation ; Sub-Saharan Africa ; chronic low back pain (cLBP) ; genetics ; personalized treatment ; polymorphism ; CYP450 ; tacrolimus ; CYP3A5 ; liver transplant ; pharmacogenomic ; minority ; data collection ; drug ; biomarker ; pharmacogenetics ; pharmacogenetic test ; personalized medicine ; gene expression ; infliximab ; adalimumab ; ulcerative colitis ; Crohn disease ; inflammatory bowel disease ; n/a ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MJ Clinical & internal medicine
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    Qualitative and Quantitative Analysis of Bioactive Natural Products 2018 (2021)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2024-04-05
    Description: Throughout most of history, medicinal plants and their active metabolites have represented a valuable source of compounds used to prevent and to cure several diseases. Interest in natural compounds is still high as they represent a source of novel biologically/pharmacologically active compounds. Due to their high structural diversity and complexity, they are interesting structural scaffolds that can offer promising candidates for the study of new drugs, functional foods, and food additives.Plant extracts are a highly complex mixture of compounds and qualitative and quantitative analyses are necessary to ensure their quality. Furthermore, greener methods of extraction and analysis are needed today.This book is based on articles submitted for publication in the Special Issue entitled “Qualitative and Quantitative Analysis of Bioactive Natural Products” that collected original research and reviews on these topics.
    Keywords: QH301-705.5 ; Q1-390 ; Scorzonera ; capsaicinoids ; artificial neural network ; cerebral ischemia reperfusion injury ; antioxidant activity ; quality evaluation ; chemometrics ; secondary metabolites ; identification ; antioxidant capacity ; Moroccan region ; volatile compounds ; HPLC-Q-Exactive-Orbitrap-MS ; quantitative analysis ; amino acids content ; HPLC-ELSD ; antioxidant ; autophagy ; quantification ; sugars ; 1-triacontanol ; hemp seed oil ; Alzheimer’s disease ; macrodiolides ; extraction ; recycling preparative high performance liquid chromatography ; HPLC methods ; GC-MS ; Myristica fragrans ; Rossa da inverno sel. Rojo Duro onion cultivar ; fruit powders ; decursin ; food traceability ; ionic liquids ; separation optimisation ; Spondias spp. ; C-glycosylflavone ; wine ; UPLC-MS ; scutellarein ; saffron ; carotenoids ; red cabbage ; hydrodistillation ; Ginkgo biloba Extract (GBE) ; gas chromatography ; organic acids ; olive leaves ; crocins ; CBD oil ; Bolbostemma paniculatum ; UPLC-ESI-MS/MS ; geographical origin ; HPLC ; traditional Chinese medicine decoction ; liquid chromatography ; bioactive natural compounds ; Podospermum ; metabolic profiling ; SPME-GC/MS ; LTQ-Orbitrap ; oral administration ; UPLC ; bioactive compounds ; Erigeron breviscapus extract ; terrain conditions ; nutmeg ; antibacterial activity ; method validation ; ShenFu prescription decoction ; chili ; decursinol angelate ; statistical evaluations ; stereoselective and simultaneous analysis ; curcuminoids ; Talaromyces pinophilus ; talarodiolide ; HPLC-Q-TOF-MS/MS ; Olea europaea L. ; triterpenes ; chromatogram-bioactivity correlation ; essential oil ; stability ; Staphylococcus aureus ; Iris lactea Pall. var. chinensis (Fisch.) Koidz. ; endothelial function ; anthocyanins ; HPLC analysis ; liquid chromatography-mass spectrometry ; nodakenin ; turmerone ; UHPLC-MS/MS ; Quercus acuta leaf ; Curcuma longa ; UHPLC analysis ; ginseng berry extract ; geographical variation ; qualitative analysis ; Sorbus ; free radical-scavenging ; ginsenosides ; flavonoids ; biostimulant ; GC/MS ; terpenes ; aleuritolic acid ; phenolic compounds ; apoptosis ; response surface methodology ; phenolic acids ; pharmacokinetics ; mass spectrometry ; scutellarin ; multivariate statistical analysis ; phenolics ; MODDE experimental design ; proanthocyanidins ; UFLC-QQQ-MS ; rice ; cannabidiol ; odor-activity values ; UPLC-QTOF-MS ; turmeric ; decursinol ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
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    Current Insights on Lipid-Based Nanosystems 2023 (2024)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2024-01-08
    Description: Lipid-based nanosystems, including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), cationic lipid nanoparticles, nanoemulsions, and liposomes, have been extensively studied to improve drug delivery through different administration routes. The main advantages linked to these systems are the ability to protect, transport, and control the release of lipophilic and hydrophilic molecules (either small molecular weight or macromolecules); the use of generally recognized as safe (GRAS) excipients that minimize the toxicity of the formulations; and the possibility to modulate pharmacokinetics and enable the site-specific delivery of encapsulated payloads. In addition, the versatility of lipid-based nanosystems has been further demonstrated through the delivery of vaccines, protection of cosmetic actives, or improvement in the moisturizing properties of cosmetic formulations. Currently, lipid-based nanosystems are well established, and there are already different commercially approved formulations for different human disorders. This success has actually paved the way to diversifying the pipeline of development, upon addressing unmet medical needs for several indications, such as cancer; neurological disorders; and autoimmune, genetic, and infectious diseases. This Special Issue aims to update readers on the latest research on lipid-based nanosystems, both at the preclinical and clinical levels.
    Keywords: design of experiment ; porcine mucous membrane ; ophthalmic tissues ; permeation ; nanostructured lipid carriers ; gentiopicroside ; phospholipid complex ; self-nanoemulsion drug delivery system ; oral bioavailability ; pharmacokinetics ; antioxidants ; marine bio-waste ; bioactive compounds ; neurodegenerative diseases ; NLC ; solid lipid nanoparticles ; SLN ; intranasal administration ; nose-to-brain ; exosome ; drug loading ; exosomal delivery ; large-scale production ; lipid nanoparticles ; mucoadhesion ; ocular bioavailability ; surface modification ; liposomes ; baricitinib ; JAK-inhibitor ; transepidermal delivery ; skin permeation ; lipid NPs ; breast cancer ; siRNA delivery ; gene silencing ; personalized therapy ; bimatoprost ; central composite design ; glaucoma ; HET-CAM test ; solid lipid nanoparticles (SLNs) ; perillyl acid ; biodistribution ; empty lipid nanoparticles ; reactogenicity ; xenobiotics ; ionizable lipids ; isoniazid ; in vivo pharmacokinetics ; drug release profile ; histopathological toxicity ; mannosylation ; nanocarriers ; Chagas disease ; Trypanosoma cruzi ; in vivo assays ; quality by design ; plumbagin ; diabetes ; in vitro ; niosomes ; levosulpiride ; antidepressant ; acute toxicity ; in vivo imaging ; bioavailability ; cisplatin ; co-encapsulation ; mifepristone ; synergism ; gefitinib ; lipid ; surfactant ; stability ; breast cancer cell ; MTT assay ; anticancer ; n/a ; bic Book Industry Communication::T Technology, engineering, agriculture::TB Technology: general issues
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    Preclinical Evaluation of Lipid-Based Nanosystems (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2024-04-09
    Description: The use of lipid-based nanosystems, including lipid nanoparticles (solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC)), nanoemulsions, and liposomes, among others, is widespread. Several researchers have described the advantages of different applications of these nanosystems. For instance, they can increase the targeting and bioavailability of drugs, improving therapeutic effects. Their use in the cosmetic field is also promising, owing to their moisturizing properties and ability to protect labile cosmetic actives. Thus, it is surprising that only a few lipid-based nanosystems have reached the market. This can be explained by the strict regulatory requirements of medicines and the occurrence of unexpected in vivo failure, which highlights the need to conduct more preclinical studies.Current research is focused on testing the in vitro, ex vivo, and in vivo efficacy of lipid-based nanosystems to predict their clinical performance. However, there is a lack of method validation, which compromises the comparison between different studies.This book brings together the latest research and reviews that report on in vitro, ex vivo, and in vivo preclinical studies using lipid-based nanosystems. Readers can find up-to-date information on the most common experiments performed to predict the clinical behavior of lipid-based nanosystems. A series of 15 research articles and a review are presented, with authors from 15 different countries, which demonstrates the universality of the investigations that have been carried out in this area.
    Keywords: nanostructured lipid carriers (NLC) ; formulation optimization ; rivastigmine ; quality by design (QbD) ; nasal route ; nose-to-brain ; N-alkylisatin ; liposome ; urokinase plasminogen activator ; PAI-2 ; SerpinB2 ; breast cancer ; liposomes ; target delivery nanosystem ; FZD10 protein ; colon cancer therapy ; supersaturation ; silica-lipid hybrid ; spray drying ; lipolysis ; lipid-based formulation ; fenofibrate ; mesoporous silica ; oral drug delivery ; hyaluronic acid ; drug release ; light activation ; stability ; mobility ; biocorona ; dissolution enhancement ; phospholipids ; solid dosage forms ; porous microparticles ; nanoemulsion(s) ; phase-behavior ; DoE ; D-optimal design ; vegetable oils ; non-ionic surfactants ; efavirenz ; flaxseed oil ; nanostructured lipid carriers ; nanocarrier ; docohexaenoic acid ; neuroprotection ; neuroinflammation ; fluconazole ; Box‒Behnken design ; nanotransfersome ; ulcer index ; zone of inhibition ; rheological behavior ; ex vivo permeation ; nanomedicine ; cancer ; doxorubicin ; melanoma ; drug delivery ; ultrasound contrast agents ; phospholipid coating ; ligand distribution ; cholesterol ; acoustic response ; microbubble ; lipid phase ; dialysis ; ammonia ; intoxication ; cyanocobalamin ; vitamin B12 ; atopic dermatitis ; psoriasis ; transferosomes ; lipid vesicles ; skin topical delivery ; oligonucleotide ; self-emulsifying drug delivery systems ; hydrophobic ion pairing ; intestinal permeation enhancers ; Caco-2 monolayer ; clarithromycin ; solid lipid nanoparticles ; optimization ; permeation ; pharmacokinetics ; follicular targeting ; dexamethasone ; alopecia areata ; lipomers ; lipid polymer hybrid nanocapsules ; biodistribution ; skin ; ethyl cellulose ; n/a ; thema EDItEUR::T Technology, Engineering, Agriculture, Industrial processes::TB Technology: general issues
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    Ophthalmic Drug Delivery, 2nd Edition (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2023-11-30
    Description: Research in ophthalmic drug delivery has developed significant advances in the few last years, and efforts have been made to develop more effective topical formulations to increase drug bioavailability, efficiency, and safety. Drug delivery to the posterior segment of the eye remains a great challenge in the pharmaceutical industry due to the complexity and particularity of the eye's anatomy and physiology. Some advances have been made with the purpose of maintaining constant drug levels in the site of action. The anatomical ocular barriers have a great impact on drug pharmacokinetics and, subsequently, on the pharmacological effect.Despite the increasing interest in efficiently reaching the posterior segment of the eye with reduced adverse effects, there is still a need to expand the knowledge of ocular pharmacokinetics that allow the development of safer and more innovative drug delivery systems. These novel approaches may greatly improve the lives of patients with ocular pathologies.
    Keywords: ocular ; drug delivery ; pharmacokinetics ; tissue isolation ; rat ; eye ; drug concentration ; method ; pigment ; melanin ; aniridia ; ataluren ; ophthalmic solution ; rare disease ; stability ; tacrolimus ; hydroxypropyl-β-cyclodextrin ; topical ophthalmic administration ; eye drops ; uveitis ; PET/CT imaging ; ocular implants ; electrospinning technique ; glaucoma ; sustained drug release ; poly ε-caprolactone ; electrospun fibers ; permeability ; retina ; retinal pigment epithelium ; Ussing chamber ; intravitreal half-life ; posterior capsule opacification ; pathophysiology ; wound healing ; lens epithelial cells ; intraocular lenses ; experimental models ; clinical studies ; gold nanoparticles ; anterior chamber ; distribution ; intracameral injection ; trabecular meshwork ; hyaluronic acid ; liposomes ; intravitreal ; ocular drug delivery ; retinal explants ; amantadine ; blood–retinal barrier ; retinal disease ; NMDA receptor ; inner BRB ; retinal capitally endothelial cells ; outer BRB ; retinal pigment epithelial cells ; transporter ; rivoceranib ; drug repositioning ; microsphere ; subfoveal choroidal neovascularization ; macular degeneration ; endotoxin-induced uveitis ; interleukins ; immunosuppressants ; physicochemical stability ; container-content interaction ; leachable compound ; nanoparticles ; PLGA ; lactoferrin ; nanoprecipitation ; protein nanocarriers ; keratoconus ; corneal ecstatic disorder ; posterior capsular opacification ; intraocular lens ; surface modification ; photothermal therapy ; photodynamic therapy ; micro-pattern ; anti-biofouling ; ocular hypertension ; prostaglandin analogues ; aqueous solubility ; chemical stability ; intraocular pressure ; cystinosis ; ophthalmic administration ; cysteamine ; compounded formulation ; PET ; nanocrystals ; conjunctivitis ; besifloxacin ; Povacoat® ; fluoroquinolones ; acanthamoeba keratitis ; controlled drug delivery ; contact lens ; miltefosine ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KND Manufacturing industries::KNDP Pharmaceutical industries
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    Clinical Pharmacology and Pharmacy of Antimicrobial Agents (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2023-11-30
    Description: In this Special Issue, our aim was to collect studies on clinical pharmacology and pharmacy of antimicrobial agents from both human and veterinary medicine as the complex problem of AMR requires actions taken within the One Health approach that involve both fields. Studies covered here are about new or optimized usage of already authorized antimicrobials, as well as discoveries about new agents, new combinations of drugs, and drug repositioning. Pharmacodynamic, pharmacokinetic, and toxicological aspects of individual and combinational drug use are areas covered in this Special Issue.
    Keywords: antibiotic combination ; minimum inhibitory concentration ; Monte Carlo ; synergistic effect ; antibiotics ; combination therapy ; multi-drug resistant infection ; meta-analysis ; pan-genome ; Campylobacter ureolyticus ; UDP-3-O-acyl-N-acetylglucosamine deacetylase ; LpxC ; campylobacteriosis ; self-medication ; students ; habits ; cystic fibrosis ; P. aeruginosa ; transporters ; Escherichia coli ; suture ; antimicrobial ; pharmacodynamics ; triclosan ; surgical site infection ; time-kill ; contact killing ; translational modelling ; antifungals ; adverse drug reaction (ADR) ; drug-drug interaction (DDI) ; polypharmacy ; multimorbidity ; intensive care patients ; traumatology ; elderly patients ; organ failure ; multi-organ failure ; drug safety ; patient safety ; nonlinear mixed-effects modeling ; glomerular filtration rate ; dosing regimen ; oxacillin ; Monte Carlo simulations ; adsorption ; desorption ; doxycycline ; pH dependence ; small ruminant feed ; heterocyclic compounds ; phenolic compounds ; pyran ; food microbiology ; microbial pathogen ; serum/plasma concentrations ; interstitial concentrations ; tissue concentrations ; pharmacokinetics ; macrolide antibiotics ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MM Other branches of medicine::MMG Pharmacology
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    Cocoa, Chocolate and Human Health (2021)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2024-04-05
    Description: This book entitled “Cocoa, Chocolate, and Human Health” presents the most recent findings about cocoa and health in 14 peer-reviewed chapters including nine original contributions and five reviews from cocoa experts around the world. Bioavailability and metabolism of the main cocoa polyphenols, i.e., the flavanols like epicatechin, are presented including metabolites like valerolactones that are formed by the gut microbiome. Many studies, including intervention studies or epidemiological observations, do not focus on single compounds, but on cocoa as a whole. This proves the effectiveness of cocoa as a functional food. A positive influence of cocoa on hearing problems, exercise performance, and metabolic syndrome is discussed with mixed results; the results about exercise performance are contradictive. Evidence shows that cocoa flavanols may modulate some risk factors related to metabolic syndrome such as hypertension and disorders in glucose and lipid metabolism. However, several cardiometabolic parameters in type 2 diabetics were not affected by a flavanol-rich cocoa powder as simultaneous treatment with pharmaceuticals might have negated the effect of cocoa. The putative health-promoting components of cocoa are altered during processing like fermentation, drying, and roasting of cocoa beans. Chocolate, the most popular cocoa product, shows remarkable losses in polyphenols and vitamin E during 18 months of storage.
    Keywords: QH301-705.5 ; Q1-390 ; TX341-641 ; n/a ; lipids ; theobromine ; colonic bacteria ; ?-glucosidase inhibition ; cacao ; tinnitus ; antioxidant capacity ; metabolomics ; methylxanthines ; lipid status ; physical exercise ; skeletal muscle ; functional volatile compounds ; soluble cocoa products ; blood pressure ; flavanols ; functional food ; classification ; monitoring ; cocoa ; yeast ; quality ; flavanols bioavailability ; fermentation ; cocoa processing ; hearing loss ; Italian chocolate ; chocolate ; (?)-catechin ; extraction and characterization methods ; heath potentials ; CREB ; inflammation ; flavanol-rich cocoa ; behavior ; (?)-epicatechin ; BDNF ; plasma appearance ; flavan-3-ol stereoisomers ; fermentation-related enzymes ; angiotensin-converting enzyme (ACE) inhibitory activity ; type 2 diabetes ; CaMKII ; exercise performance ; anti-inflammatory properties ; (+)-catechin ; bioactive compounds ; chiral separation ; plasma ; oxidative stress ; antidiabetic capacity ; polyphenols ; oligopeptides ; urine ; protein–phenol interactions ; postprandial ; working memory ; procyanidins ; simulated gastrointestinal digestion ; cocoa-based ingredients ; one-compartment model ; cocoa beans ; athlete ; biomarkers ; polyphenol ; metabolic syndrome ; nutrition ; bioavailability ; roasting ; glucose metabolism ; cohort study ; plasma nutrikinetics ; pharmacokinetics ; human ; cocoa proteins ; metabolites ; cocoa by-product ; meal ; bioactive peptides ; performance ; liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry (LC-ESI-QToF-MS) ; starter culture ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
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    Drug-Drug Interactions (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2022-06-24
    Description: Drug–drug interactions (DDIs) cause a drug to affect other drugs, leading to reduced drug efficacy or increased toxicity of the affected drug. Some well-known interactions are known to be the cause of adverse drug reactions (ADRs) that are life threatening to the patient. Traditionally, DDI have been evaluated around the selective action of drugs on specific CYP enzymes. The interaction of drugs with CYP remains very important in drug interactions but, recently, other important mechanisms have also been studied as contributing to drug interaction including transport- or UDP-glucuronyltransferase as a Phase II reaction-mediated DDI. In addition, novel mechanisms of regulating DDIs can also be suggested. In the case of the substance targeted for interaction, not only the DDIs but also the herb–drug or food–drug interactions have been reported to be clinically relevant in terms of adverse side effects. Reporting examples of drug interactions on a marketed drug or studies on new mechanisms will be very helpful for preventing the side effects of the patient taking these drugs. This Special Issue aims to highlight current progress in understanding both the clinical and nonclinical interactions of commercial drugs and the elucidation of the mechanisms of drug interactions.
    Keywords: tadalafil ; ticagrelor ; drug-drug interaction ; pharmacokinetics ; plasma concentration ; CYP3A4 ; Loxoprofen ; CYP3A ; Dexamethasone ; Ketoconazole ; CYP2D6 ; O-desmethyltramadol ; physiologically-based pharmacokinetics ; tramadol ; (‒)-sophoranone ; CYP2C9 ; potent inhibition ; in vitro ; in vivo ; drug interaction ; low permeability ; high plasma protein binding ; biflavonoid ; cytochrome P450 ; drug interactions ; selamariscina A ; uridine 5′-diphosphoglucuronosyl transferase ; tissue-specific ; systemic exposure ; P-glycoprotein (P-gp) ; organic anion transporting polypeptide 1A2 (OATP1A2) ; Rumex acetosa ; fexofenadine ; chronic kidney disease ; drug–drug interactions ; polypharmacy ; adverse drug reactions ; Lexicomp ; subset analysis ; signal detection algorithms ; spontaneous reporting systems ; mechanism-based inhibition ; competitive inhibition ; non-competitive inhibition ; substrate ; inhibitor ; cytochromes P450 ; OATP1B1 ; OATP1B3 ; tyrosine kinase inhibitors ; drug-drug interactions ; migraine ; lasmiditan ; gepants ; monoclonal antibodies ; CYP1A1 ; CYP1A2 ; drug–drug interaction ; expression ; metabolism ; regulation ; drug transporter ; ubiquitination ; ixazomib ; DDI ; computational prediction ; in silico ; QSAR ; drug metabolism ; ADME ; CYP ; metabolic DDI ; P450 ; 1A2 ; 2B6 ; 2C19 ; 2C8 ; 2C9 ; 2D6 ; 3A4 ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences
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    Carotenoids (2021)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2024-04-05
    Description: Carotenoids are a group of natural pigments, consisting of more than 750 compounds. They are mostly yellow, orange, or red in color, due to the system of conjugated double bonds. This structural element is also responsible for the good antioxidant properties of many carotenoids. Carotenoids have shown numerous biological activities (not only as provitamin A), e.g., preventive properties of fruits and vegetables. As lipophilic compounds, their uptake and storage in the body are dependent on various conditions. In vitro and in vivo data showed stimulating and inhibitory effects of matrix compounds on bioaccessibility and bioavailability of carotenoids.
    Keywords: QH301-705.5 ; Q1-390 ; singlet-triplet annihilation ; silicon carotenoids ; dye-sensitized solar cells ; spent coffee grounds ; astaxanthin ; antioxidant antagonism ; carotenoid and chlorophyll derivatives ; fluorocarotenoids ; RNS ; feed processing ; ?-carotene ; iodocarotenoids ; hydrophilic ; selenium carotenoids ; free radical kinetics ; mechanisms ; stability ; free radicals ; antioxidant ; soil amendment ; pressurized fluid extraction ; extraction ; metal ions ; lutein ; lettuce ; lycopene ; antioxidant synergism ; iron carotenoids ; ROS ; solubility ; flavonoids ; bromocarotenoids ; sulfur carotenoids ; marine carotenoids ; cationic lipid ; carotenoids ; antioxidants ; nelfinavir ; fruit ; SK-Hep-1 ; carotenoid ; storage ; vegetables ; ethanol ; exon skipping ; inflammation ; xanthophylls ; Duchenne muscular dystrophy ; pharmacokinetics ; carrots ; chlorocarotenoids ; chelating compound ; cardiovascular disease ; ageing ; accelerated solvent extraction ; nitrogen carotenoids ; VEGF ; chlorophyll ; liquid chromatography ; antiradical ; PEG conjugates ; injection solvent ; cycloaddition ; HIV ; esterification ; antisense oligonucleotide ; B16F10 ; interaction ; cancer chemoprevention ; antireductant ; PC-3 ; oxidative stress ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
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    From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2022-08-12
    Description: This book collects contributions published in the Special Issue “From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential” and dealing with successful stories of drug improvement or design using classic protocols, quantum mechanical mechanistic investigation, or hybrid approaches such as QM/MM or QM/ML (machine learning). In the last two decades, computer-aided modeling has strongly supported scientists’ intuition to design functional molecules. High-throughput screening protocols, mainly based on classical mechanics’ atomistic potentials, are largely employed in biology and medicinal chemistry studies with the aim of simulating drug-likeness and bioactivity in terms of efficient binding to the target receptors. The advantages of this approach are quick outcomes, the possibility of repurposing commercially available drugs, consolidated protocols, and the availability of large databases. On the other hand, these studies do not intrinsically provide reactivity information, which requires quantum mechanical methodologies that are only applicable to significantly smaller and simplified systems at present. These latter studies focus on the drug itself, considering the chemical properties related to its structural features and motifs. Overall, such simulations provide necessary insights for a better understanding of the chemistry principles that rule the diseases at the molecular level, as well as possible mechanisms for restoring the physiological equilibrium.
    Keywords: SARS-CoV-2 ; benzoic acid derivatives ; gallic acid ; molecular docking ; reactivity parameters ; selenoxide elimination ; one-pot ; imine-enamine ; reaction mechanism ; DFT calculations ; selenium ; anti-inflammatory drugs ; QSAR ; pain management ; cyclooxygenase ; multitarget drug ; cannabinoid ; neuropathic pain ; clopidogrel ; NMR study ; oxone ; peroxymonosulfate ; sodium halide ; thienopyridine ; drug discovery ; precision medicine ; pharmacodynamics ; pharmacokinetics ; coronavirus SARS-CoV-2 ; COVID-19 ; 3-chymotrypsin-like protease ; pyrimidonic pharmaceuticals ; molecular dynamics simulations ; binding free energy ; β-carrageenan ; antioxidant activity ; Box-Behken ; extraction ; Eucheuma gelatinae ; physic-chemistry ; rheology ; quercetin ; quercetin 3-O-glucuronide ; cisplatin ; nephrotoxicity ; cytoprotection ; lithium therapy ; neurocytology ; toxicology ; neuroprotection ; chemoinformatics ; big data ; methadone hydrochloride ; pharmaceutical solutions ; drug compounding ; high performance liquid chromatography ; stability study ; microbiology ; fucoidan ; alginate ; L-selectin ; E-selectin ; MCP-1 ; ICAM-1 ; THP-1 macrophage ; monocyte migration ; protein binding ; breast milk ; M/P ratio ; statistical modeling ; molecular descriptors ; chromatographic descriptors ; affinity chromatography ; anti-ACE ; anti-DPP-IV ; gastrointestinal digestion ; in silico ; molecular dynamics ; paramyosin ; seafood ; target fishing ; n/a ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MM Other branches of medicine::MMG Pharmacology
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    Novel Strategies in the Development of New Therapies, Drug Substances and Drug Carriers 2.0 (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2023-09-11
    Keywords: drug design and discovery ; drug&ndash ; protein interactions ; drug response ; drug solubility ; antimicrobial drugs ; antiviral drugs ; antibiotics ; anticancer drugs ; cancer prevention ; molecular modeling ; molecular mechanisms ; crystallography ; preclinical study ; pharmacokinetics ; pharmacodynamics ; pharmacognosy ; nuclear receptors ; receptor agonist and antagonist ; activity profiling, markers and diagnostics ; drug carriers ; dosage form ; nanoparticles ; dissolution testing ; bic Book Industry Communication::M Medicine::MB Medicine: general issues::MBG Medical equipment & techniques
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    Novel Anticancer Strategies (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2023-04-05
    Description: Novel Anticancer Strategies reviews important findings and updates within the cancer therapy field, of great interest to those in academic research studying the development and validation of novel anticancer approaches. The Editor invited preeminent specialists to contribute to original and review articles devoted to key areas of major progress and expectations. Key features: Nanoparticle-based drug delivery in cancer therapy; Extracellular vesicles for anticancer drug delivery; Peptide-based drug conjugates; Cancer stem cells as a valuable target to eradicate tumor relapse; Spheroids in preclinical model for cancer research; and cancer immunotherapy.
    Keywords: tumor-homing extracellular vesicles ; pH-sensitive extracellular vesicles ; doxorubicin ; tumor therapy ; pancreatic cancer ; targeted tumor therapy ; homing peptide ; antitumor peptide conjugates ; daunomycin ; oxime linkage ; combinatorial immunotherapy ; cytotoxics ; biomarkers ; precision medicine ; immunotherapy ; anti-PD-L1 ; ionizing irradiation ; pharmacokinetics ; tumor-immune interaction ; global sensitivity ; immuno-oncology ; mathematical modeling ; glycol chitosan nanoparticle ; high-intensity focused ultrasound ; deep tumor penetration ; dense ECM ; cancer treatment ; prostate cancer ; gastrin-releasing peptide receptor ; RM26 ; albumin-binding domain ; targeted therapy ; gastrin-releasing peptide receptors (GRPR) antagonist ; cervical cancer ; tetraarsenic hexoxide ; patient-derived xenograft ; autophagy ; cisplatin ; fenbendazole ; micelle solubilization ; Soluplus® polymeric micelles ; toxicity test ; sonoporation ; microbubbles ; ultrasound ; intracellular signaling ; phosphorylation ; ultrasound contrast agents ; drug delivery ; cellular stress ; tumour microenvironment ; cancer stem cells ; extracellular vesicles ; drug delivery systems ; liposomes ; immunoliposomes ; antisense oligonucleotides ; 3D cultures ; tumor microenvironment ; tumor spheroids ; efficacy analysis ; drug resistance ; cancer therapy ; glioblastoma ; receptor tyrosine kinases ; epidermal growth factor receptor ; small molecule inhibitors ; nanoformulations ; breast cancer ; micelles ; dendrimers ; anticancer drugs ; platinum drug ; methotrexate ; lung metastasis ; liver metastasis ; cancer treatments and progression biomarkers ; mesoporous silica nanoparticles ; controlled release ; anticancer natural prodrugs ; natural products ; cancer targeting ; nanoformulations/nanomedicine applications ; n/a ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MJ Clinical & internal medicine::MJC Diseases & disorders::MJCL Oncology
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    Micro/Nanofluidic and Lab-on-a-Chip Devices for Biomedical Applications (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2024-03-31
    Description: Recently, microfluidic, nanofluidic and lab-on-a-chip devices have gained particular attention in biomedical applications. Due to their advantages, such as miniaturization, versatility, ease of use, cost-effectiveness, and the potential to replace animal models for drug development and testing, these devices hold tremendous potential to revolutionize the research of more effective treatments for several diseases that threaten human life. With integrated biosensors, these devices allow the development and design of micro- and nanoparticles to be studied in detail, modelling human physiology, investigating the molecular and cellular mechanisms underlying disease formation and progression, and gaining insights into the performance and long-term effects of responsive drug delivery nanocarriers. This Special Issue gathered research papers, and review articles focusing on novel microfluidic, nanofluidic and lab-on-a-chip devices for biomedical applications, addressing all steps related to fabrication, biosensor integration and development, characterization, numerical simulations and validation of the devices, optimization and, the translation of these devices from research labs to industry settings.
    Keywords: protein biomarker ; microarray ; microfluidic cassette ; multiplex measurement ; immunoassay ; point-of-care testing ; microfluidic device ; small intestine ; ex vivo ; histology ; embedded resin ; sectioning ; peptide biosensor ; lab-on-a-chip ; label-free detection ; peptide aptamers ; protein biomarkers ; microfluidic biochip ; troponin T ; computational simulations ; drug discovery ; organ-on-a-chip ; microfluidic devices ; preclinical models ; numerical simulations ; automation ; non-enzymatic ; DNA amplification ; L-DNA ; microfluidic ; fluorescence ; paper microfluidics ; sweat ; sensing ; hydrogels ; lactate ; osmotic pumping ; evaporation ; capillary ; wicking ; biochemical assay ; microfluidics ; cell trap ; RBC ; evolutionary algorithm ; generative design ; artificial intelligence ; organ-on-chip ; liver-on-chip ; liver disease ; multi-level microfluidic device ; live cell imaging ; long-term microscopy imaging ; focus drifting ; immersion oil viscosity ; bacterial population dynamics ; single-cell studies ; E. coli ; mother machine ; computational fluid dynamics ; cancer-on-chip ; xenograft ; colorectal cancer ; pharmacodynamics ; pharmacokinetics ; drug efficacy ; oxaliplatin ; microfabrication ; microphysiological system ; biophysical stimuli ; biochemical stimuli ; in vitro cell culture ; cortical neurons ; hippocampal neurons ; electrical stimulation ; Micro-Electrode Arrays ; engineered neuronal networks ; polydimethylsiloxane ; microchannels ; in vivo micro bioreactor ; additive manufacturing ; poly-(ethylene glycol)-diacrylate ; biocompatibility ; COVID-19 ; diagnosis ; image analysis ; PCR ; SARS-CoV-2 ; n/a ; thema EDItEUR::M Medicine and Nursing
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    Recent Advances in Antibody Therapeutics (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2022-07-06
    Description: Since first receiving approval in 1986, antibody-based therapeutics have been the most successful modality for the treatment of various diseases. This Special Issue of IJMS, “Recent Advances in Antibody Therapeutics”, presents leading-edge articles and reviews for discovery, development, and clinical applications of therapeutic antibodies, covering antibody drug conjugates (ADCs), GPCR-targeting antibodies, a functional antibody screening, bioassay of bispecific antibodies, antibody applications for cardiovascular diseases, antibody delivery to CNS, etc. The excellent studies in this Special Issue would valuable insight for scientists and clinicians in the field of therapeutic antibodies
    Keywords: interleukin 33 ; ST2 receptor ; scFv ; C2_2E12 ; bladder cancer ; antibodies ; immune checkpoint inhibitors ; antibody-drug conjugates ; sacituzumab govitecan ; enfortumab vedotin ; erdafitinib ; cost-effectiveness ; G protein-coupled receptor ; membrane protein ; antigen ; therapeutic antibody ; anti-angiogenesis ; delta-like ligand ; irinotecan ; paclitaxel ; VEGF ; SARS-CoV-2 ; spike protein ; receptor-binding domain ; phage display ; monoclonal antibody ; cytomegalovirus ; peptide/major histocompatibility complex class I complex ; T-cell-receptor-like antibody ; affinity maturation ; yeast surface display ; combinatorial antibody library ; agonist antibody ; cell fate ; bispecific antibodies ; bioassays ; mechanisms of action ; binding assays ; potency assays ; atherosclerosis ; inflammation ; antibody therapy ; blood–brain barrier ; antibody ; pharmacokinetics ; disposition ; biochemical and physicochemical properties ; Fc binding ; receptor-mediated transcytosis ; brain shuttle ; molecular Trojan horse ; transferrin ; anti-cancer antibody ; antibody engineering ; biophysical properties ; computational methods ; research cell bank ; antibody therapeutics ; recombinant antibodies ; intracellular antibodies ; single-chain antibody fragment ; nanobody ; Human papillomaviruses ; HPV oncoproteins ; HPV-associated cancer ; HPV cancer therapy ; asthma ; refractory asthma ; biomarker ; n/a ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PN Chemistry
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    Sustainable Functional Food Processing (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2022-10-25
    Description: Functional nutrition is deeply connected with healthy lifestyle and sustainable food production, due to its positive health benefits and the use of economically underexplored and natural raw materials. Expectedly, it appeals to large number of interested consumers while becoming lucrative segment of the food industry with a fast-growing market fueled by new sociodemographic trends. Accordingly, functional juices and beverages made of indigenous fruits are interesting niche for various food market stakeholders. Here, biologically active compounds (BACs) and probiotics that have positive health effects in functional foods (juices) are mostly thermolabile. This is especially important for industry that still employs classical heat treatments (e.g., pasteurization), while being concerned with degradation of food quality in the final products. To prevent this, focus is on designing economic and ecological technologies that are able to preserve nutritional and sensory quality while maintaining microbiological stability in products. Such approaches are based on low-energy consumption and low-impact processing, e.g. “hurdle technology” that combines advanced and conventional methods (e.g., high-power ultrasound, pulse electric field). Food design is another important focus point for consumers’ sensory appeal and economic success of foods. Hence, technologies as 3D food printing can be particularly useful for manufacturing. Based on the above, presented topics are relevant to sustainable functional food production, functional fruit juices, BACs, “hurdle technology,” advanced food processing, 3D food printing, and authentic fruits.
    Keywords: dehydration ; conserving vegetables ; improving shelf-life ; rehydrated pepper ; histological preparation ; green practices ; meat analogue ; liquid additives ; soy protein isolate ; lecithin ; emulsion ; functional fruit juice ; hurdle technology ; non-thermal processing ; preservation ; quality ; probiotic ; fruit by-products ; lulo bagasse powder ; fiber ; antioxidant properties ; carotenoids ; cocoa shell ; high voltage electrical discharge ; tannin ; dietary fiber ; water binding capacity ; grindability ; traditional ; slow ; pressure and microwave cooking ; polyphenols ; antioxidant activity ; faba bean ; lentil ; pea ; probiotic safety ; toxicity ; pathogenicity ; functional food industry ; pharmacological interactions ; functional fruit juices ; mushroom ; vitamin D ; reducing capacity ; glycation ; Lactuca sativa ; metabolomics ; antioxidants ; eustress ; total soluble solids ; particle size distribution ; total anthocyanin content ; antioxidant capacity ; non-dairy beverages ; pulses ; chickpea ; lupin ; flow behavior ; animal and plant proteins ; computer vision system ; nutritional value ; texture ; water activity ; viscosity ; microstructure ; heavy metals ; amino acids ; pesticide ; fruit wastes ; vegetable wastes ; drying ; extraction ; intensification technologies ; phenolic acids ; food processing ; minimally processed foods ; UHLPC-MS/MS ; sous-vide cooking ; vegetables ; seafood ; cephalopods ; safety ; nutritive quality ; beetroot ; convective drying ; infrared drying ; purée ; Fourier-transform infrared spectroscopy ; confocal scanning microscopy ; fruit juice ; interaction ; drug ; phytochemical ; pharmacokinetics ; ginger ; pineapple ; turmeric ; juice mix ; physicochemical properties ; microbiological quality ; sensory attributes ; Diospyros kaki ; post-harvest losses ; dehydrated persimmon ; thin-layer modeling ; drying rate ; old apple cultivar ; biologically active compounds ; functional food ; agriculture ; extensive farming ; bisphosphonates ; SERMs ; food ; supplements ; bioavailability ; meal ; coffee ; juice ; mineral water ; edible mushroom ; nutrition ; phenolic compounds ; vacuum ; poria cubes ; optimization ; stage drying ; n/a ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences ; bic Book Industry Communication::T Technology, engineering, agriculture
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    State of the Art in Separation Science (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2022-10-25
    Description: In this Topical Collection, ten articles (one review and nine research articles) are published in a time span of 2021–2022. All articles are written by experts in the field of Separation Techniques who were invited to contribute to the presentation of the current status in separation science. The authors were invited to answer the questions: What is the state-of-the-art in Separation Sciences? What advances have been reported recently? Last but not least, what are the future perspectives? The Editor and authors hope that the readers will find valuable information in the topic.
    Keywords: protein-based chiral stationary phase ; alpha 1-acid glycoprotein ; chiral recognition mechanism ; molecular docking ; proteomics ; high-performance liquid chromatography ; mass spectrometry ; gout ; uric acid ; Salvia miltiorrhiza ; HPLC-MS/MS ; pharmacokinetics ; wine-processed ; hydrophilic interaction liquid chromatography ; chromatography ; oligopeptides ; acetyl hexapeptide-8 ; acetyl hexapeptide-3 ; Argireline ; cosmetics ; SARS-CoV-2 ; virus particles ; air filtering ; aerosols ; probability distributions ; rotational particle separator ; air separation ; steam methane reforming ; water gas shift ; alternative fluids ; gas turbine ; Senecio anteuphorbium ; response factors ; true quantitation ; allelopathy ; herbicide ; chlorpropham ; potato ; μQuEChERS/UHPLC-PDA ; validation ; cooking ; methyl nicotinate ; methyl salicylate ; ethyl salicylate ; 2-hydroxyethyl salicylate ; pain relief spray ; Tulasnellaceae sp. ; Gymnadenia orchidis ; mdium-pressure liquid chromatography ; reversed-phase liquid chromatography ; ergosterol ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PN Chemistry
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    Progress and Recent Advances in Solid Organ Transplantation (2022)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2022-06-21
    Description: There have been recent significant improvements in the short-term survival of solid organ transplantation patients due to advances in immunosuppression and transplant techniques. However, long-term graft survival has still lagged behind other outcomes and has now become one of the main problems in solid organ transplantation.For this Special Issue, we invited researchers and clinicians to submit studies on solid organ transplantation. These have provided us with additional knowledge and skills that will ultimately help us to improve outcomes after solid organ transplantation.
    Keywords: living donation ; nephrectomy ; hand-assisted laparoscopic nephrectomy ; body composition ; complications ; simultaneous pancreas-kidney transplantation ; immunosuppression ; graft order ; sequence ; outcome ; survival ; kidney transplantation ; hydrogen ; diarrhea ; small intestinal bacterial overgrowth ; sickle cell disease ; sickle cell ; transplantation ; outcomes ; big data ; tacrolimus ; metabolism ; C/D ratio ; cholesterol ; dyslipidemia ; LDL-C ; liver transplantation ; hematuria ; chronic kidney disease ; tocilizumab ; clazakizumab ; desensitization ; anti-HLA alloantibody ; post traumatic growth ; psychiatric morbidity ; network analysis ; ESAS ; MINI ; CPC ; DCPR ; distress ; demoralization ; alexithymia ; anxiety ; antibody-mediated rejection ; recurrent primary disease ; renal transplantation ; pancreas transplantation ; cold ischemia time ; delayed graft function ; Eurotransplant Senior Program ; end-stage renal disease ; intensive care unit ; bioimpedance analysis ; drug dosing ; lean body mass index ; pharmacokinetics ; tacrolimus C/D ratio ; mineral bone disorder ; parathyroidectomy ; parathyroid hormone ; osteoporosis ; bone fractures ; Contrast-enhanced ultrasound ; kidney perfusion ; kidney function ; kidney donation ; n/a ; bic Book Industry Communication::M Medicine ; bic Book Industry Communication::M Medicine::MM Other branches of medicine::MMG Pharmacology
    Language: English
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    Drug Delivery Technology Development in Canada (2021)
    MDPI - Multidisciplinary Digital Publishing Institute
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    Publication Date: 2023-12-21
    Description: Canada continues to have a rich history of ground-breaking research in drug delivery within academic institutions, pharmaceutical industry and the biotechnology community.
    Keywords: R5-920 ; RM1-950 ; encapsulation ; biodistribution ; pharmaceutics ; targeted therapies ; gambogic acid ; GE11 peptide ; formulation and dosage form development ; transient modulation ; ROESY NMR spectroscopy ; bioaccessibility ; polymeric micelle ; pharmacological Inhibitors of HIF-1 and STAT3 ; nanoparticles ; Vitamin D ; drug discovery ; EGFR-targeted therapy ; translational research ; clinical trials ; doxorubicin ; dissolution ; drug development ; permeation enhancers ; Canada ; plant ; primary central nervous system lymphomas ; photostabilizers ; head and neck squamous cell carcinoma ; mouse models ; drug delivery systems ; melphalan ; hypoxia-induced chemoresistance ; skin ; virus ; circadian clock ; child friendly formulation ; adenanthin ; co-delivery ; canola oil deodorizer distillate ; Metaplex ; innovation ; controlled drug delivery ; nifedipine ; radiolabeling ; amphotericin B ; biological barriers ; blood-brain barrier (BBB) ; biologicals ; lipid nanoparticles ; oral formulation ; phytosterols ; medical devices ; chronotherapy ; oral ; cationic gemini surfactant ; route of administration ; drug delivery ; intra-arterial chemotherapy ; developing world ; sustained delivery ; water miscible solvents ; combination therapy ; antibodies ; throughput ; magnetic fields ; liposomes ; medulloblastoma ; drug-resistant melanoma ; rosmarinic acid ; topical formulation ; TNO gastrointestinal model ; gastrointestinal simulator ; malignant gliomas ; transdermal drug delivery ; oral delivery ; precision medicine ; 3D spheroid ; flavonoids ; staurosporine ; DOX-Vit D ; loading gradients ; bacteriophage ; phospholipid complex ; triggered drug release ; HIF-1 ; phage display ; pharmacokinetics ; emulsion ; quercetin ; cisplatin ; parasitic infections ; remote loading ; HAV6 cadherin peptide ; blood-brain barrier ; inclusion complex ; tocopherols ; STAT3 ; ultrasound ; liposome ; fungal infections ; magnetic resonance imaging (MRI) ; MG63 ; model orange juice ; radiation ; cancer ; mefloquine ; small molecules ; bic Book Industry Communication::M Medicine
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    Glutathione: Chemistry and Biochemistry (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2023-09-11
    Description: It has been known that cellular glutathione content and its speciation play a role, among others, in redox homeostasis, cell cycle control, immunological defense, and pathological abnormalities. Furthermore, it plays a significant role in the biotransformation of drugs and other endogenous or exogenous electrophilic species. Most of these cellular functions are related to the thiol function of the cysteine moiety.This reprint presents the publications that appeared in the Special Issue of Molecules, “Glutathione: Chemistry and Biochemistry.” The first three contributions review the present-day knowledge of the GSH/GSSG system and the most important GSH-related proteins involved in regulating various cellular events. The subsequent four contributions present selected interventions that modulate the GSSG/2GSH system. One of the contributions to this session describes a new HPLC method to quantify the reduced and oxidized glutathione levels. The third session involves three contributions demonstrating the role of GSH in the metabolism of different candidate and clinically used anticancer drugs. One of the contributions, a theoretical work, provides helpful information for developing GSH analogs with high ACE inhibitor activity.By purpose and content, this Special Issue is addressed to the vast number of life science researchers (academic and industrial) and medical professionals who are interested in or already engaged in research that involves glutathione.
    Keywords: cyclophosphamide ; autoimmune diseases ; glutathione ; glutathione-S-transferase ; polymorphism ; glutaredoxin ; iron-sulfur cluster ; iron ; S-glutathionylation ; S-nitrosylation ; GSH ; nitrosoglutathione ; redox-regulation ; polymerized whey protein ; physicochemical properties ; pharmacokinetics ; toxicity ; chalcone ; cysteine ; thiols ; Michael addition ; diastereoselective addition ; reactive oxygen species ; oxidative stress ; nanotoxicity ; cell injury ; fluorescence probes ; brain ; liquid chromatography ; diode array detector ; anticancer drugs ; mechanisms of glutathione conjugation reaction ; detoxification ; bioactivation ; sulodexide ; endothelial cells ; ischemia ; apoptosis ; GSSG ; GCLc ; GSS ; redox potential ; supramolecular arrangement ; M06-2X/6-311++G(d,p) ; DFT ; molecular docking ; angiotensin-converting enzyme ; cell ; redox homeostasis ; glutathionylation ; glutathione system ; glutathione enzyme ; n/a ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GP Research & information: general ; bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences
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    On the Road to Precision Medicine: Magnetic Systems for Tissue Regeneration, Drug Delivery, Imaging, and Theranostics (2023)
    MDPI - Multidisciplinary Digital Publishing Institute
    Details
    Publication Date: 2023-09-11
    Keywords: iron oxide magnetic nanoparticles ; silica coating ; magnetic hyperthermia ; cancer cells ; alamar blue ; neutral red ; A549 ; A35 ; BJ ; ultrasmall magnetic iron oxide nanoparticles ; inflammatory pain ; analgesia ; pro-inflammatory cytokines ; neurotoxicity ; long-term potentiation ; solid lipid nanoparticles ; magnetic nanoparticles ; magnetic solid lipid nanoparticles ; cancer theranostics ; MRI-contrast agents ; pulsed laser ablation in liquids ; multimodal imaging ; MRI ; CT ; photothermal therapy ; iron-gold nanoparticles ; pharmacokinetics ; magnetic targeting ; micro-systems ; nano-systems ; drug delivery ; nanoparticles ; microparticles ; targeted delivery ; magnetic guidance ; theranostics ; imaging ; AC biosuceptometry ; cirrhosis-associated rat hepatocarcinogenesis ; nanotechnology ; magnetoresponsive nanocomposite ; functional coating ; particle targeting ; particle aggregation ; stent targeting ; nanomedicine ; MRI technology ; patient-centred healthcare ; iron oxide nanoparticles ; paramagnetic salinomycin complexes ; bacterial ghosts ; gadolinium ; manganese ; lectin ; PLGA ; ConA ; magnetic polymer nanoparticles ; MPQ ; allografts ; photodynamic therapy ; IR775 ; image-guided therapy ; n/a ; bic Book Industry Communication::T Technology, engineering, agriculture::TB Technology: general issues
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  • 42
    Electronic Resource
    Electronic Resource
    Human Interindividual Variability in Parameters Related to Health Risks (1999)
    Springer
    Risk analysis 19 (1999), S. 711-726 
    Details
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007045922532
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  • 43
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    Electronic Resource
    Evaluation of the Uncertainty in an Oral Reference Dose for Methylmercury Due to Interindividual Variability in Pharmacokinetics (1999)
    Springer
    Risk analysis 19 (1999), S. 547-558 
    Details
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 μg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 μg/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 μg/kg/day and an MRL of 0.3 μg/kg/day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007017116171
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  • 44
    Electronic Resource
    Electronic Resource
    Das Rückstandsverhalten von Chloramphenicol nach intramuskulärer Applikation beim Schwein (1985)
    Springer
    European journal of nutrition 24 (1985), S. 113-119 
    Details
    ISSN: 1436-6215
    Keywords: Chloramphenicol ; pharmacokinetics ; residue ; pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary Residues of Chloramphenicol (CAP) were examined in 24 pigs after intramuscular injection of 30 mg CAP/kg body weight. Two pigs were slaughtered after 3, 6, 12,18, 24, 36 hours, 2, 3, 6, 10, 21 and 30 days, respectively. CAP-concentrations were determined in muscle, blood, urine, liver, kidney, bile, and fat. Methods used were gas-liquid chromatography and radioimmunoassay. Detection limits reached were 1−5 ppb. The concentration-time curves obtained reflected a long elimination phase and allowed only calculation of this half-life. Elimination half-life was estimated to be for muscle, blood and urine 160–170 hours, for kidney 310 and for bile 250 hours. Significant correlations were found to exist between CAP-concentrations in plasma and muscle. It appears that blood would be a good body fluid for monitoring CAP-residues in tissue.
    Notes: Zusammenfassung Zur Untersuchung des Rückstandsverhaltens von Chloramphenicol (CAP) wurden 24 Mastschweine, 24–28 Wochen alt, intramuskulär mit 30 mg CAP/kg Körpergewicht behandelt und je 2 Tiere nach 3, 6, 12, 18, 24, 36 Stunden, 2, 3, 6, 10, 21 und 30 Tagen geschlachtet. Die CAP-Gehalte in Muskulatur, Blut, Urin, Leber, Niere, Galle und Fett wurden gaschromatographisch und radioimmunologisch bestimmt. Die Nachweisgrenze beider Methoden liegt in Abhängigkeit von der Matrix zwischen 1 und 5 ppb. Die erhaltenen Kinetiken weisen eine terminale Elimination auf, deren Halbwertszeiten für Muskulatur, Blut und Urin ca. 160–170 Stunden, für Niere 310 Stunden und für Galle 250 Stunden betragen. Die CAP-Konzentration in Muskulatur und Blut weisen eine signifikante, lineare Korrelation auf. Blutuntersuchungen könnten deshalb als Screening-Methode bei umfangreichen Rückstandskontrollen eingesetzt werden.
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    URL: http://dx.doi.org/10.1007/BF02020458
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  • 45
    Electronic Resource
    Electronic Resource
    Enzymatic and pharmacokinetic studies on the metabolism of branched chain α-keto acids in the rat (1983)
    Springer
    European journal of nutrition 22 (1983), S. 14-26 
    Details
    ISSN: 1436-6215
    Keywords: branched chain α-keto acids ; 4-methyl-2-oxopentanoate, 3-methyl-2-oxopentanoate ; 3-methyl-2-oxobutyrate ; dehydrogenation ; transamination ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Michaelis-Konstanten und Aktivitäten von Dehydrogenasen und Transaminasen der drei verzweigten α-Ketosäuren Keto-Valin, Keto-Leucin und Keto-Isoleucin in Leber, Niere, Skeletmuskel und Gehirn von Ratten werden mitgeteilt. Nach oraler Zufuhr passieren nur 11–22% der Ketosäuren unverändert die Leber. Aus pharmakokinetischen und Resorptions-Untersuchungen erhaltene Blutspiegel an Ketosäuren werden zu den Michaelis-Konstanten in Beziehung gesetzt. Bei den geringen Konzentrationen an Ketosäuren nach oraler Zufuhr kann angenommen werden, daß die oxidativen Prozesse in den nichthepatischen Geweben über die Transaminierung überwiegen. Daten über die Wachstumseffizienz von verzweigtkettigen α-Ketosäuren im Vergleich zu den entsprechenden Aminosäuren stimmen mit dieser Vorstellung überein. Bei intravenöser Verabreichung müßten die Voraussetzungen für Transaminierung besser sein als nach oraler Zufuhr. Auf der Basis von Daten aus der Literatur werden die Übertragbarkeit unserer Befunde auf den Menschen und die verschiedenen Faktoren, welche die Effizienz der verzweigten α-Ketosäuren durch Einwirkung auf ihren Stoffwechsel beeinflussen können, diskutiert.
    Notes: Summary Miehaelis-constants and enzyme activities for dehydrogenation and transamination of the three branched chainα-keto acids in liver, kidney, skeletal muscle, and brain of rats are reported. After oral load only 11–22 % of the keto acids pass the liver unchanged. Blood levels in pharmacokinetic and absorption studies are related to the Michaelis-constants. At the low keto-acid concentrations after oral application, dehydrogenation in the non-hepatic tissues is supposed to prevail over transamination. Data on feed efficiency of branched chain α-keto acids reported in the literature support this view. The chance for transamination is better after intravenous administration. The transferability of our data to humans, and various factors influencing the efficiency of branched chain α-keto acids are discussed in connection with data reported in the literature.
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    URL: http://dx.doi.org/10.1007/BF02020781
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  • 46
    Electronic Resource
    Electronic Resource
    The lymphatic route. 1) Albumin and hyaluronidase modify the normal distribution of interferon in lymph and plasma (1986)
    Springer
    Cellular and molecular life sciences 42 (1986), S. 432-433 
    Details
    ISSN: 1420-9071
    Keywords: Interferon ; immunomodulator ; catabolism ; pharmacokinetics ; administration routes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary When human recombinant interferon-α2 diluted in saline was injected s.c. into rabbits, the total amount recovered in thoracic lymph was less than 0.4%. Recoveries increased from 2- to 8-fold if interferon was injected in 4% albumin or with hyaluronidase, respectively. Albumin added to interferon acts as an interstitial fluid expander, thus favoring interferon absorption through lymphatics rather than blood capillaries. This strategy may increase the therapeutic index of interferon.
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    URL: http://dx.doi.org/10.1007/BF02118644
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  • 47
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and absolute bioavailability of salbutamol in healthy adult volunteers (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 631-634 
    Details
    ISSN: 1432-1041
    Keywords: salbutamol ; albuterol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salbutamol was administered to sixteen healthy male volunteers intravenously and by mouth in liquid, tablet, and capsule form using a Latin-Squares design. Pharmacokinetic parameters from intravenous data were similar to previously reported values obtained with oral administration, with a mean terminal half-life of 3.8 h and a mean clearance of 439 ml·min−1·1.73 m−2. Peak plasma concentrations of 10–20 ng·ml−1 were obtained 1–3 h following oral administration. The absolute bioavailability of each of the oral preparations was 44%. While statistically significant differences in lag time and time to peak concentration were noted among the various oral preparations, the drug is rapidly absorbed in all three dosage forms and the observed differences are unlikely to be of clinical significance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02456001
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  • 48
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    Electronic Resource
    Pharmacokinetics of rufloxacin in healthy volunteers (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 101-105 
    Details
    ISSN: 1432-1041
    Keywords: Rufloxacin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma and urine kinetics of rufloxacin were assessed in healthy volunteers after single (100, 200, 400 and 800 mg) and multiple (300 mg followed by 150 mg daily, Group 1, and 400 mg followed by 200 mg daily, Group 2) oral doses. The kinetics of a single oral dose of 800 mg was assessed in fasting and non-fasting subjects to assess the influence of food intake on drug absorption. The AUCs were 134, 266 and 375 μg · h · ml−1 after 100, 200 and 400 mg, respectively. The AUC after 800 mg p. o. was 715 μg · h · ml −1 in fasting subjects and 614 μg · h · ml−1 in non-fasting subjects. The parameters of the model and the mean renal clearance values indicated some departure from linearity in rufloxacin kinetics. After multiple doses the plasma drug levels during the 6th treatment day were similar to those after the first dose in Group 1 and were about 30–40% higher after the first dose in Group 2. The half-lives after the last dose were much shorter than those estimated in the single dose studies (33–36 h and 50–80 h, respectively).
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    URL: http://dx.doi.org/10.1007/BF00314928
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  • 49
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of meropenem in subjects with renal insufficiency (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 535-538 
    Details
    ISSN: 1432-1041
    Keywords: Meropenem ; Carbapenem ; pharmacokinetics ; uraemia ; haemodialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 24 or 48 h. Meropenem concentrations in plasma and urine were measured by a microbiological assay. The mean peak plasma concentration of meropenem ranged from 28 to 40 μg·ml−1 and was not affected by the degree of renal impairment. The terminal half-life of meropenem was approximately 1 h in subjects with normal kidney function and it was proportionately increased as renal function decreased. A significant linear relationship between total body clearance and creatinine clearance as well as between renal clearance and creatinine clearance was observed. The mean apparent volume of distribution at steady state was not significantly altered in uraemic patients. The mean cumulative urinary recovery of meropenem in healthy volunteers was 77% of the administered dose and it was significantly decreased in patients with renal impairment. Haemodialysis shortened the elimination half-life, from 9.7 h during the predialysis period to 1.4 h during the dialysis period. The dose of meropenem should be reduced in relation to the decrease in creatinine clearance.
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    URL: http://dx.doi.org/10.1007/BF00314864
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  • 50
    Electronic Resource
    Electronic Resource
    Comparative pharmacokinetics of ceftazidime in young, healthy and elderly, acutely ill males (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 179-186 
    Details
    ISSN: 1432-1041
    Keywords: ceftazidime ; pharmacokinetics ; elderly patients ; young volunteers ; acute infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ceftazidime have been investigated after single and multiple i.v. doses in 9 young healthy male volunteers and 15 elderly male patients with acute bacterial infections. All subjects had normal, age-correlated glomerular function. Distribution and elimination in young volunteers were unaffected by posture and were similar to what has been reported earlier. In contrast, elderly patients had longer t1/2β (3.1 vs 1.9 h), larger AUC (414.0 vs 276.6 h·mg/l), lower total and renal clearances, reduced urinary recovery over 12 h and enlarged Vss. Total serum clearance of ceftazidime was closely correlated with the51Cr-EDTA clearance. There was no significant change in51Cr-EDTA clearance after seven days of treatment. A reduction in the dose of betalactam antibiotics eliminated by the kidney is advisable in elderly patients with an acute bacterial infection.
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    URL: http://dx.doi.org/10.1007/BF00614556
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    Pharmacokinetics of mefloquine in the presence of primaquine (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 559-560 
    Details
    ISSN: 1432-1041
    Keywords: Mefloquine ; Thai subjects ; pharmacokinetics ; Primaquine ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314870
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  • 52
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    Electronic Resource
    The effect of exercise on atropine pharmacokinetics (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 395-397 
    Details
    ISSN: 1432-1041
    Keywords: atropine ; exercise ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven healthy males (19–32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO2 max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1. Ex prior to atropine (T2) significantly decreased the mean volume of distribution (Vz, 278 vs 2321). Ex in T3 significantly decreased the serum half life (t1/2, 4.2 vs 3.5 h), Vz (278 vs 1981), and clearance (CL, 763 vs 638 ml·min−1) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng·ml−1) and area under the curve (AUC, 44.1 vs 53.1 ng·ml−1). In T5, Ex significantly decreased the t1/2 (3.4 h), Vz (182 l) and CL (575 ml·min−1) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min−1), elimination rate constant (ke, 0.0012 vs 0.0015 min−1), Cp (14 ng·ml−1) and AUC (53.3 ng·h·ml−1). These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.
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    URL: http://dx.doi.org/10.1007/BF00315417
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    Pharmacokinetics of diphemanil methylsulphate in healthy subjects (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 689-691 
    Details
    ISSN: 1432-1041
    Keywords: Diphemanil methylsulphate ; pharmacokinetics ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of oral diphemanil methylsulphate have been evaluated in six healthy male volunteers. Absorption of the drug was slow (tmax=2 to 4 h), the mean half-life was 8.35 h, and the amount of the drug recovered in urine within 48 h ranged from 0.6 to 7.4% of the administered dose. The results suggest low bioavailability, assuming that the drug is poorly metabolized.
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    URL: http://dx.doi.org/10.1007/BF00265939
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    Dose proportionality study of loperamide following oral administration of loperamide oxide (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 693-694 
    Details
    ISSN: 1432-1041
    Keywords: Loperamide ; loperamide oxide ; diarrhoea ; pharmacokinetics ; dose-proportionality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of loperamide, after oral administration of increasing doses (1 to 16 mg) of loperamide oxide, has been investigated in 10 healthy male volunteers, using a randomised cross-over design. Comparison of the maximum plasma loperamide concentration and AUC demonstrated that the bioavailability of loperamide was proportional to the dose of loperamide oxide administered.
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    Clinical pharmacokinetics and tolerability of alpidem in healthy subjects given increasing single doses (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 369-374 
    Details
    ISSN: 1432-1041
    Keywords: Alpidem ; Anxiolytics ; pharmacokinetics ; tolerance ; metabolites ; sedation ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, placebo-controlled, crossover experiment in 21 healthy male volunteers, aged 19 to 27 y, the pharmacokinetics and tolerance of the new anxiolytic drug alpidem (SL80.0342) and its three major metabolites were studied after single doses of 25, 50, 100 and 200 mg. Plasma concentrations of alpidem (in 20 subjects) and metabolites (in 6 subjects) were measured by HPLC over a period of 54 h after dosing. Cmax, tmax and AUC(0–54) and, when possible, t1/2 were determined for alpidem and metabolites and the dose linearity of the parameters was investigated. The time to peak of alpidem was dose independent in most subjects and was short (1–4 h); the mean values at the four dosing levels were 1.9, 1.7, 1.6 and 1.8 h. The peak concentration increased with the dose, the mean values being 17, 34, 88 and 115 ng · ml−1, respectively. In 50% of the subjects cmax tended to stabilize between the 100 and 200 mg dose. Dose linearity was also present for the AUC, which plateaued between the 100 and 200 mg dose in only 3 out of 20 subjects; the mean AUC was 119, 281, 669 and 1117 ng · ml−1 · h, respectively. The apparent half-life of elimination appeared to be dose independent, mean values at the increasing dosing levels being 18.7, 19.9, 18,1 and 17.9 h. A similar relationship between the kinetics parameters and dose of the alpidem was observed for the metabolites SL83.0912, SL80.0522 and SL83.0725. The formation of metabolites was not saturated as their AUCs relative to corresponding alpidem AUCs were not dose related. Thus the kinetics of alpidem and its three major metabolites were linear after doses of 25 to 200 mg. The drug was well tolerated by most of the subjects. Sedation and dizziness occurred mainly after the 100 and 200 mg doses.
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    URL: http://dx.doi.org/10.1007/BF00314970
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    Evaluation of the accuracy of a pharmacokinetically-based patient-controlled analgesia system (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 67-75 
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    ISSN: 1432-1041
    Keywords: Morphine ; Patient-controlled analgesia ; opioids ; pharmacokinetics ; bolus-elimination-transfer ; computer-assisted continuous infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bone marrow transplant patients having severe, prolonged oral mucositis pain (expected to last for one to three weeks) used a computer-controlled infusion system to self-administer morphine for pain control. Individual patient pharmacokinetic information, derived from a pretreatment bolus morphine dose, was used in a new bolus-elimination transfer algorithm to produce rapid adjustments of steady plasma morphine concentrations when the patient requested more or less drug. We evaluated the performance characteristics (bias and precision) of this pharmacokinetically based patient-controlled analgesic infusion system (PKPCA) in a group of 15 cancer patients over six to 14 days. Although we found a three- to fivefold pharmaco-kinetic variability in the tailoring morphine dose data, the PKPCA system was free of systematic bias (insignificant overall prediction error) during the patient-controlled infusions in this study population. The absolute prediction error was 19.9% for the group on the first study day and 25.6% over the entire study period (aggregate results; 6–14 days of continuous use). Two-thirds of the patients exhibited no bias throughout the study period, and individual bias in the others was symmetrically distributed (three patients with underpredictions and two overpredicted). Magnitude of prediction error during the patient-controlled morphine infusions was not related to the magnitude of pharmacokinetic deviation of individual subjects from group parameters. Our results indicate that this PKPCA system provides accurate control of plasma morphine concentration when used by patients to self-administer opioid for prolonged pain relief continuously over 1 to 2 weeks. Use of individual pharmacokinetic information, instead of population parameters, may account for superior performance characteristic of this computer-assisted continuous drug infusion system.
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    URL: http://dx.doi.org/10.1007/BF02280757
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    Steady state pharmacokinetic profile of indomethacin in elderly patients and young volunteers (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 77-80 
    Details
    ISSN: 1432-1041
    Keywords: Indomethacin ; steady-state ; pharmacokinetics ; elderly
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state pharmacokinetic profile of indomethacin was examined in twelve healthy volunteers (4 m, 8 f; 20–34 y) and in 12 elderly subjects (7 m, 5 f; 70–88 y). Two formulations of indomethacin were examined, providing duplicate data for each subject group. The subjects received each formulation of indomethacin (25 mg tid) for 6 days in a single blind crossover fashion. On day 7, after an overnight fast, a final 25 mg dose of indomethacin was given and plasma concentrations measured over the following 12 h. Kinetic parameters Cpmin, tmx and AUC (0–12 h) were determined. There were no differences in the pharmacokinetic parameters between young and elderly subjects or between data for the two formulations of indomethacin. AUC values (μg · ml−1 · h), for example, for the two formulations in the young subjects were 5.85 and 6.85 while the values for the elderly subjects were 6.55 and 6.50 respectively. When each treatment period was considered independently there was a significant difference between young and elderly subjects with regard to compliance. The rates of non compliance (over and under compliance) using a capsule count technique were, however, low with a mean maximum value of 5.8% being recorded for the elderly subjects.
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    Pharmacokinetics of caffeine in patients with decompensated type I and type II diabetes mellitus (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 449-452 
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    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; Caffeine ; pharmacokinetics ; P-450 mono-oxygenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Diabetes may alter the pharmacokinetics of aminopyrine and antipyrine, which are used to assess liver function. Caffeine has recently been used to test liver function, but the effect of diabetes on caffeine kinetics is not known. The kinetics of caffeine has been examined in patients with decompensated Type I and Type II diabetes and in two age- and sex-matched control groups. In both types of diabetes the apparent caffeine clearance, half-life, and apparent volume of distribution were similar to controls. It is concluded that decompensated diabetes does not influence the cytochrome P-448 mono-oxygenase system responsible for caffeine metabolism.
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    URL: http://dx.doi.org/10.1007/BF00626367
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    Pharmacokinetics and dialysability of isradipine in chronic haemodialysis patients (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 231-233 
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    ISSN: 1432-1041
    Keywords: Isradipine ; Haemodialysis ; pharmacokinetics ; dialysability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of isradipine, a calcium-channel blocker, have been studied in eight patients on chronic haemodialysis. A single oral dose of 5 mg was administered on both a non-haemodialysis and a haemodialysis day and the plasma concentrations of isradipine were analyzed. The mean cmax, tmax, AUC, and t1/2 in plasma on the non-haemodialysis day were 5.2 ng·ml−1, 1.4 h, 23.8 ng·h·ml−1, and 3.1 h, respectively. The dialysis clearance of isradipine was negligible (5.0 ml·min−1). The t1/2 values during haemodialysis were not significantly different from those observed during the same period post dose on the non-haemodialysis day. The study demonstrates that supplemental doses of isradipine are not necessary in these patients since isradipine is not significantly removed by haemodialysis.
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    URL: http://dx.doi.org/10.1007/BF00278492
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    Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 247-253 
    Details
    ISSN: 1432-1041
    Keywords: Liver cirrhosis ; Spirapril ; ACE inhibitor ; pharmacokinetics ; haemodynamic effects ; liver function tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensinconverting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n=10), in patients with chronic, non-cirrhotic liver disease (n=8) and in a control group of healthy subjects (n=16). The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 μg·h·l−1, 923 μg·h·l−1 and 1300 μg·h·l−1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively. Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h−1 in patients vs. 2.00 h−1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls. Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.
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    Dopamine pharmacokinetics in critically ill newborn infants (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 593-597 
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    ISSN: 1432-1041
    Keywords: Dopamine ; Newborns ; critically ill patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5–20 μg · kg−1 · min−1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013–0.3 μg/ml. Total body clearance averaged 115 ml · kg−1 · min−1. The apparent volume of distribution and elimination half life averaged 1.8 1 · kg−1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.
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    The concentration-dependent disposition and kinetics of inulin (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 619-624 
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    ISSN: 1432-1041
    Keywords: Inulin ; pharmacokinetics ; half life ; distribution ; concentration-dependent clearance ; healthy subjects ; chronic renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of inulin was studied in 30 healthy male and 10 healthy female volunteers, and 10 patients with stable chronic renal failure (mean creatinine clearance 45 ml·min−1) following intravenous infusion of 70 mg·kg−1 over 5 min. Plasma concentrations fell rapidly initially but the rate of decline decreased continuously over 8 h and a linear terminal elimination phase could not be identified. Inulin was excreted rapidly by the subjects with normal renal function and 97.3% of the dose was recovered in the urine in 8 h. There was a progressive highly significant fall in the renal clearance of inulin after 2 h as plasma concentrations fell below about 150 mg·l−1. Six to 8 h after administration the clearance was less than 50% of the initial value in the healthy volunteers and the corresponding fall in the renal patients was 33%. The concentration-dependent renal clearance of inulin was confirmed in “step-up” and “step-down” constant infusion studies in which clearances were measured at mean plasma concentrations ranging from 35.2 to 186.7 mg·l−1. These studies virtually excluded time, changes in posture and urine flow rate as important factors. There was no statistically significant fall in clearance during the first 2 h and kinetic analysis was based on data obtained over this time. Under these conditions the mean plasma half life, volume of distribution (Vss) and total body clearance of inulin in the healthy males, healthy females and patients with chronic renal failure were 73.2, 65.5 and 172.4 min, 10.5, 9.6 and 8.81·70 kg−1 and 113.3, 111.5 and 43.3 ml·min−1·70 kg−1 respectively. There were no sex differences in any of the kinetic variables. The mechanism of the concentration-dependent clearance of inulin is unknown but the findings are consistent with saturable renal tubular reabsorption. Care is required with the use of inulin for measurement of the glomerular filtration rate by the single injection technique.
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    Effect of ampicillin on mefloquine pharmacokinetics in thai males (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 631-633 
    Details
    ISSN: 1432-1041
    Keywords: Mefloquine ; ampicillin ; Thai subjects ; pharmacokinetics ; enterohepatic recycling ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single oral dose of mefloquine given either alone or with ampicillin has been studied in 8 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with ampicillin (1648 vs 1228 ng·ml−1), as well as a significantly reduced terminal half life (15.3 vs 17.7 days), mean residence time (20.1 vs 23.4 days) and volume of distribution at steady state (14.1 vs 19.4 l·kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 5 days was significantly increased by ampicillin (4.86 vs 3.27 μg·ml−1 day). These changes in mefloquine disposition after antibiotic treatment may be due both to an increase in fractional bioavailability and a reduction in the enterohepatic recycling of mefloquine.
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    Lack of effect of multiple dose sucralfate on the pharmacokinetics of roxatidine acetate (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 637-638 
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    ISSN: 1432-1041
    Keywords: Roxatidine acetate ; sucraflate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00279987
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    Modelling circadian variation in the pharmacokinetics of non-steroidal anti-inflammatory drugs (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 357-361 
    Details
    ISSN: 1432-1041
    Keywords: Circadian rhythms ; Indomethacin ; Ketoprofen ; pharmacokinetics ; time-varying models ; nonsteroidal anti-inflammatory drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A one-compartment model with first-order absorption has provided good fits to five sets of indomethacin data and four sets of ketoprofen data taken at different times of day. There was substantial variation in the model parameters with time of administration and most of the features of this variation applied equally to both drugs. From the data examined, the source of variation appears to be mainly in the absorption phase and this was confirmed using a chronokinetic analysis, in which simultaneous fits were obtained with time-variant rate parameters. However, there may also be circadian variation in protein binding. The danger of quoting parameter values for either of these two drugs based on administration at a single time of day has been illustrated, and this may well be true for other drugs.
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    Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 353-356 
    Details
    ISSN: 1432-1041
    Keywords: Gamma-hydroxybutyric acid ; pharmacokinetics ; dose-proportionality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg−1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.
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    Comparison of the effects of two different galenical preparations of glyceryl trinitrate on pulmonary artery pressure and on the finger pulse curve (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 451-456 
    Details
    ISSN: 1432-1041
    Keywords: Glyceryl trinitrate spray ; pharmacokinetics ; a/b-ratio ; pulmonary artery diastolic pressure ; finger pulse curve ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course and the magnitude of the effect of glyceryl trinitrate (GTN) on central venous (pulmonary artery diastolic pressure-PAPd) and peripheral arterial (a/b-ratio of the finger pulse wave) haemodynamics were compared in a randomized double-blind cross-over study in 12 patients suffering from congestive heart failure (NYHA II–III) with elevated PADd at rest (≥15 mm Hg). The data were obtained in a bioavailability study of two sprays of glyceryl trinitrate, which differed in their galenical characteristics and in the dose of GTN (0.4 mg vs. 0.8 mg). Following sublingual administration of each spray, PAPd, a/b-ratio and the plasma concentrations of GTN and its metabolites were measured up to 30 min. The relative bioavailability of GTN of the test preparation was estimated to be 157%, 161% and 147%, when calculated from the plasma concentration-time data or the integrated effect of GTN on a/b-ratio or PAPd, respectively. The mean time courses of the decrease in PAPd and the increase in the a/b-ratio of the finger pulse curve were mirror images. Thus, there was a strong correlation between the mean values of PAPd and a/b-ratio following the administration of glyceryl trinitrate. Since the slope of the relationship differed considerably between the patients, the magnitude of effect of GTN on PAPd in the individual patient could not be predicted from the changes in a/b-ratio.
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    Pharmacokinetics and pharmacodynamics of benazepril hydrochloride in patients with major proteinuria (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 463-466 
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    ISSN: 1432-1041
    Keywords: Benazepril ; Proteinuria ; benazeprilat ; ACE inhibitor ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with proteinuria by studying 8 patients with major proteinuria of different causes who were given a single dose of 10 mg p.o. The maximum plasma concentration of benazepril was found between 0.5 and 2 h after dosing (median 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were observed between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives of 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater in the patients. Plasma ACE was completely inhibited from 1.5 to 6 h after dosing, and at 48 h the mean inhibition was still 42 %. Plasma renin showed substantial intersubject variation. Mean supine blood pressure (systolic/diastolic) was reduced from baseline by a maximum of 18/13 mm Hg at 6 h. Proteinuria was diminished after benazepril in 7 patients. In conclusion, the results of this study suggest that proteinuria in the nephrotic range does not require a change in benazepril dosage.
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    Absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin from different regions of the gastrointestinal tract in man (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 473-476 
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    ISSN: 1432-1041
    Keywords: dDAVP ; bioavailability ; gastrointestinal tract ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP) from different regions of the gastrointestinal (GI) tract (stomach, duodenum, jejunum, ileum, colon, rectum) has been studied in 6 healthy, male volunteers aged 24 to 35 years, followed for 12 h after each drug administration. For i. v. administration the subjects received 4 μg dDAVP. For intestinal administration 400 μg dDAVP was directly applied to six distinct sites in the GI tract via two or four channel tubes with or without a distal occlusive balloon. Biological effects were assessed and plasma and urinary levels of dDAVP were measured using a specific, sensitive RIA. Urine osmolality remained elevated and diuresis decreased for 12 h following dDAVP administration irrespective of the site of application. After i. v. administration, the half-life of elimination of dDAVP was 60.0 min, plasma clearance 1.7 ml·min−1·kg−1, amount excreted in urine 2.0 μg and renal clearance was 0.8 ml·min−1·kg−1. The mean bioavailability (f) after gastric application was 0.19% (range 0.02–0.35%). f was 0.24% after duodenal application (range 0.04–0.62%), 0.19% after jejunal (range 0.01–0.41%), 0.03% after distal ileal (range 0.01–0.08%), 0.04% after proximal colonic (range 0.01–0.12%) and 0.04% after rectal (0.01–0.10%) application. The bioavailability was significantly higher in the three upper GI regions in comparison to the three lower regions. The bioavailability of dDAVP after gastric, duodenal and jejunal application was similar to that after swallowing a tablet in a previous study. Absorption from the ileum was lower than expected and no preferential site of absorption was found.
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    Disposition of quinine in plasma, red blood cells and saliva after oral and intravenous administration to healthy adult Africans (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 171-174 
    Details
    ISSN: 1432-1041
    Keywords: Quinine ; Malaria ; pharmacokinetics ; red blood cells ; plasma ; saliva ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quinine has been studied in ten healthy adult Africans after intravenous infusion and oral ingestion of a 500 mg dose. Blood and saliva samples were collected over 48 h and quinine in plasma, red cells and saliva was determined by HPLC. Quinine was rapidly and almost completely absorbed after an oral dose, with absorption half-life of 0.53 h, a tmax of 1–3 h and a bioavailability of 88%. Analysis of the i. v. data gave an apparent volume of distribution of 3.6 1·kg−1 and a plasma clearance of 0.19 l·kg−1·h−1. The concentration-time curves for plasma, red cells and saliva had declining phases were approximately parallel, giving a similar half-life that in all three media. The half-lives after the i. v. infusion also did not different from those after oral administration. The dose was well tolerated by both methods of administration.
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    Binding of a metabolite of triflusal (2-hydroxy-4-trifluoromethylbenzoic acid) to serum proteins in rat and man (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 175-179 
    Details
    ISSN: 1432-1041
    Keywords: 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) ; Triflusal ; triflusal metabolite (HTB) ; pharmacokinetics ; protein binding ; ultrafiltration ; binding constant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) is the main active metabolite of the platelet anti-aggregant drug triflusal. Its binding to plasma proteins of rats and healthy volunteers in vitro and in vivo has been studied. Rats were given a single oral dose of 50 mg·kg−1 triflusal and the healthy volunteers received 300 mg as a single oral dose or a multiple dose regimen of 600 mg every 24 h and 300 mg every 8 h, both for 13 days. Protein-free HTB was obtained by ultrafiltration. Unbound and total HTB concentrations were determined by HPLC. HTB was primarily bound to albumin in plasma. The Scatchard plots suggested two types of binding sites for HTB on the albumin molecule. In rats, the binding constants (K=intrinsic affinity constant, n=number of binding sites) were K1=1.4×105 l·mol−1, n1=1.23, and K2=4.1×103 l·mol−1 and n2=3.77. The mean plasma concentration in rats after oral administration was 185 (37) μg·ml−1 (protein-free HTB: 2.44 (0.77)%). The binding constants in human plasma were K1=4.7×105 l·mol−1, n1=1.93, K2=4.3 l·mol−1 and n2=4.28. The plasma HTB concentration in man (n=8) was 35 μg·ml−1 (Cmax) after a single oral dose of triflusal 300 mg, 172.96 μg·ml−1 (Cmax·ss) during the multiple dosage regimen of 300 mg every 8 h, and 131 μg·ml−1 (Cmax·ss) during the multiple oral dose regimen of 600 mg every 24 h. Unbound HTB ranged from 0.27 to 0.43%, depending on dose. HTB had high affinity for plasma albumin, which was not saturable after therapeutic doses. It showed linear elimination.
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    URL: http://dx.doi.org/10.1007/BF00278480
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    Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 181-185 
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    ISSN: 1432-1041
    Keywords: Glycerol ; brain oedema ; serum ; cerebrospinal fluid ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Glycerol 50 g infused i. v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom was given 500 ml of a 10% solution IV over 4 h, serum and CSF were repeatedly sampled during and after the infusion and glycerol was measured enzymatically. The highest serum glycerol level of 191–923 mg/l was observed at the end of the infusion. The maximum CSF glycerol of 18.7–110.8 mg/l was attained 0–1 h after the end of the infusion. Elimination both from serum and CSF approximated a single-exponential decay; the elimination half-life from serum was 0.29–0.56 h compared to 1.03–3.68 h from CSF. In six of the seven cases there was a temporary reversal of the serum/CSF concentration gradient during glycerol elimination. The ratios of the AUCs of CSF and serum, which describe the overall penetration of glycerol into CSF, ranged from 0.09–0.31. In conclusion, the serum level of glycerol produced by giving 50 g IV glycerol over 4 h may not be sufficiently high reliably dehydrate to brain tissue in many patients, and the slow elimination of glycerol from the CSF may be related to the so-called rebound phenomenon.
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    URL: http://dx.doi.org/10.1007/BF00278481
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    Formation and excretion of dipyrone metabolites in man (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 187-191 
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    ISSN: 1432-1041
    Keywords: Dipyrone ; Acetylation phenotype ; metabolism ; pharmacokinetics ; urinary excretion ; metabolite clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The formation and urinary excretion of the dipyrone metabolites, methylaminoantipyrine (MAA), aminoantipyrine (AA), formylaminoantipyrine (FAA) and acetylaminoantipyrine (AAA) were determined following administration of a single oral 1.0 g dose of dipyrone to 12 healthy volunteers. The AAA/AA plasma ratio showed that 3 subjects were slow and 9 were rapid acetylators. Pharmacokinetic parameters were determined separately for each group. A good correlation was found between the plasma and urine AAA/AA ratios. The renal clearance of the four metabolites was similar for both phenotypes. A significant difference in the rate of formation of dipyrone metabolites was found for AA, 0.25 (slow) vs 0.1 ml·min−1·kg−1 (rapid), and for AAA 0.75 (slow) vs 7.53 ml·min−1·kg−1 (rapid). There were comparable differences between slow and rapid acetylators in the AUC and the urinary excretion extrapolated to infinity for AA and AAA. The present results show that the kinetics of dipyrone metabolites in plasma and urine can provide a useful measure of the activity of the enzymes involved in their production.
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    URL: http://dx.doi.org/10.1007/BF00278482
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    Effect of salbutamol on digoxin pharmacokinetics (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 197-201 
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    ISSN: 1432-1041
    Keywords: Digoxin ; Salbutamol ; serum ; skeletal muscle digoxin ; pharmacokinetics ; drug interaction ; serum potassium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of the β2-adrenoceptor agonist salbutamol has previously been shown to decrease serum digoxin concentration in healthy volunteers. A possible explanation of the phenomenon is a β2-adrenoceptor-mediated increase in the specific binding of digoxin to skeletal muscle. The present study was undertaken to further elucidate the effect of salbutamol on the pharmacokinetics of digoxin in man. Nine volunteers were studied on two occasions during salbutamol or placebo treatment. On test days salbutamol, 4 μg·kg−1·h−1 or saline was infused for 10 h, preceded and followed by four and three days, respectively, of oral administration. A single i. v. injection of digoxin 15 μg·kg−1, was given 20 min after starting the infusion. At the end of the infusion a muscle biopsy was taken from the vastus lateralis. Blood samples for the analysis of serum digoxin and potassium were repeatedly taken over 72 h. Urine was collected over a period of 24 h for determination of the renal excretion of digoxin and potassium. The serum digoxin concentration, expressed as the AUC 0–6 h was 15% lower during salbutamol infusion than during saline infusion. Salbutamol caused significantly faster elimination of digoxin from the central volume of distribution to deeper compartments. Salbutamol had no effect on the renal clearance of digoxin. The skeletal muscle digoxin concentration tended to be higher (48%) during salbutamol compared to placebo treatment. The serum potassium concentration was significantly lower after salbutamol compared to placebo, as was the rate of renal excretion of potassium. The results support the hypothesis that the salbutamol-induced decrease in serum digoxin is caused by increased distribution of digoxin to skeletal muscle (and possibly other tissues), and that this may be secondary to a β2-adrenoceptor-mediated increase in Na-K-ATPase activity.
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    URL: http://dx.doi.org/10.1007/BF00278484
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    Pharmacokinetics of nicorandil in patients with normal and impaired renal function (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 203-207 
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    ISSN: 1432-1041
    Keywords: Nicorandil ; pharmacokinetics ; angina pectoris ; uraemia ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of oral nicorandil 20 mg 12 hourly for 9 doses was evaluated in 21 hospitalized patients with angina pectoris due to coronary heart disease and with normal and impaired renal function. Patients were divided into 3 groups based on creatinine clearance (CLCr): GROUP I (n=6) 〉 80 ml/min, GROUP II (n=8) 20–80 ml/min, and GROUP III (n=7) 〈 20 ml/min. After the first dose, the total clearance of nicorandil (CL) value did not change with increasing renal failure and so was not dependent on creatinine clearance. After the last dose CL was 51 l·h−1 in Group I, 44 l·h−1 in Group II and 56 l·h−1 in Group III, and it was not related to creatinine clearance. The percentage of the dose excreted in the urine was 0.4%. No significant difference was noted in any of the other pharmacokinetic parameters examined in the three groups, not even on comparing values obtained on the first and last days of treatment. The findings suggest that there is no need to change the dose of nicorandil in subjects with different degrees of renal failure.
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    Plasma levels of oxybutynine chloride in children (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 83-85 
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    ISSN: 1432-1041
    Keywords: Enuresis ; Oxybutynine chloride ; children ; pharmacokinetics ; adverse effects ; anticholinergic actions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Anticholinergic adverse-effects in children treated with conventional doses of oxybutynine led us to measure plasma oxybutynine levels in children. 18 children, aged 5 to 13 y, who required treatment with oxybutynine chloride for daytime incontinence were studied. Plasma concentrations were measured on the fifth day of a course of treatment in which the dose was adapted to the child's body weight; the dose was given twice daily at 12-hour intervals. In 10 children aged between 5 and 8 y, the mean dose was 0.1 mg · kg−1. In 8 children aged between 10 and 13 years, the mean dose was 0.15 mg · kg−1. The highest concentration was usually found between 1 and 2 h after administration. The subsequent fall in concentration was rapid and after 6 h oxybutynine was no longer measurable in 14 of the children. The concentrations found were not different from those seen in adults given equivalent doses. The results show that plasma concentrations in children were not very different from those observed in adults if the dose were adapted to the body weight of the children. No special differences in paediatric use were revealed that might explain the particular adverse-effects. The results of the study argue against the dosage regimen proposed before these adverse events were detected. They strongly favour a dose adapted to the body weight of the child, with a 12-hour interval between doses.
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    Plasma concentrations and effect on testosterone metabolism after single doses of MK-0434, a steroid 5 alpha-reductase inhibitor, in healthy subjects (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 123-126 
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    ISSN: 1432-1041
    Keywords: Steroid 5α-reductase inhibitor ; Testosterone metabolism ; MK-0434 ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A four-period, two-panel, single-rising-dose study (0.1–100 mg) was conducted in healthy males to investigate the pharmacodynamics, tolerability and pharmacokinetics of MK-0434, a steroid 5α-reductase inhibitor. MK-0434 was associated with a significant reduction in dihydrotestosterone, which was maximal at 24 h and maintained through 48 h post treatment. The maximum reduction was approximately 50 % and occurred at all doses above 5 mg (10, 25, 50 and 100 mg). MK-0434 appeared to have no effect on serum testosterone at these single doses. Rising single doses of MK-0434 were associated with an increase in Cmax and AUC but the changes were less than proportional to dose, most likely due to nonlinear absorption. MK-0434 given in single doses up to 100 mg was without significant adverse effects in healthy male volunteers. In summary, MK-0434 is a well-tolerated, potent, orally active 5α-reductase inhibitor in man.
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    URL: http://dx.doi.org/10.1007/BF00199874
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    Cyclosporin pharmacokinetics in heart-lung transplant recipients with cystic fibrosis (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 261-265 
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    ISSN: 1432-1041
    Keywords: Cystic fibrosis ; Cyclosporin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg·kg−1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg·kg−1). The mean maximum blood concentration of CsA for the oral dose was 776 ng·ml−1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng·ml−1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.
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    Single dose pharmacokinetics of proguanil and its metabolites in pregnancy (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 247-251 
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    ISSN: 1432-1041
    Keywords: Proguanil ; Pregnancy ; Malaria ; cycloguanil ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and whole blood concentrations of proguanil, its active metabolite cycloguanil, and the inactive metabolite 4-chlorophenyl-biguanide, were measured by HPLC in 10 healthy Karen women in the last trimester of pregnancy, following a 200 mg single oral dose of proguanil. Four of these women were restudied 2 months after delivery. The pharmacokinetic properties of proguanil were similar during and after pregnancy. Median peak plasma concentrations of proguanil during pregnancy and following delivery were 212 and 215 ng·ml−1, and occurred at 4.5 and 5 h, respectively. Mean plasma AUC values for proguanil during and following pregnancy were 94 and 98 ng·h·ml−1·kg−1, respectively. Corresponding whole blood AUC values were 361 and 396 ng·h·ml−1·kg−1. The mean elimination half lives and mean residence times of proguanil in plasma and whole blood were 12.3 and 19.6 h and 13.8 and 20.7 h respectively during pregnancy. Following pregnancy these values were 17.1 and 19.7 h for plasma and 19.7 h and 20.2 h for whole blood respectively. Mean peak plasma and whole blood concentrations of cycloguanil following pregnancy were 25 and 22 ng·ml−1 respectively. During pregnancy peak cycloguanil concentrations in both plasma and whole blood were markedly lower, 13 and 12 ng ml−1, respectively. Two pregnant women (neither of whom were restudied) were probably poor metabolisers of proguanil. The mean ratio of proguanil to cycloguanil plasma AUC was 16.7 in the third trimester of pregnancy and 7.8 following pregnancy, compared with less than 5 in previously reported studies. The concentrations of 4-chlorophenylbiguanide in both plasma and whole blood in pregnant subjects were also lower than those after pregnancy. These data show that blood concentrations of the active antimalarial metabolite cycloguanil are reduced in late pregnancy and that the currently recommended dose of proguanil could be inadequate for antimalarial prophylaxis in pregnant women.
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    On the intraindividual variability and chronobiology of cyclosporine pharmacokinetics in renal transplantation (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 265-269 
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    ISSN: 1432-1041
    Keywords: Cyclosporine ; Renal transplantation ; pharmacokinetics ; intraindividual variation ; circadian variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The intraindividual variability and circadian variation of oral cyclosporine (CsA) pharmacokinetics were studied over 24 h in 18 renal transplant recipients at steady state, and in 10 of the patients during a second 24 h period. The absolute percentage intraindividual difference in daytime AUC (0–12 h) ranged from 2% to 54% (mean 30%), and the corresponding variability in nighttime AUC (0–12 h) ranged from 5% to 80% (mean 34%). The pharmacokinetic variables t1/2, tmax and Cmax were more variable than the AUC (0–12 h) both during the day and at night. The evening trough level was significantly lower than the morning trough level; 185 ng · ml−1 versus 223 ng · ml−1. This, together with a significantly longer t1/2 in the night than the day, suggested circadian variability in the pharmacokinetics of CsA. In a separate retrospective study in 162 renal transplant recipients given CsA by constant intravenous infusion, repeated CsA blood concentration measurements at steady state showed lower concentrations during the day than the night, suggesting higher CsA clearance during daytime. It is concluded that CsA pharmacokinetics in renal transplant recipients, besides the well-known interindividual variability, also displays large intraindividual variability as well as circadian variation. Our findings further emphasize the necessity and difficulty of pharmacological monitoring in the clinical use of CsA in organ transplantation.
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    Delayed disposition of adriamycin and its active metabolite in haemodialysis patients (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 301-302 
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    ISSN: 1432-1041
    Keywords: Adriamycin ; Haemodialysis ; adriamycinol ; pharmacokinetics ; moment analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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    Dose proportional absorption of 25–150 mg atenolol (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 305-306 
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    ISSN: 1432-1041
    Keywords: Atenolol ; bioavailability ; intestinal absorption ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We investigated the dose proportionality after the intake of oral atenolol 25, 50, 100 and 150 mg. Standard tablets were taken by 8 healthy volunteers in randomised order of doses. The area under the curve divided by dose did not differ between the doses, indicating that the absorption of this hydrophilic compound, with known incomplete bioavailability, was constant over the range tested.
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    Esmolol, an ultrashort-acting, selective β1-adrenoceptor antagonist: pharmacodynamic and pharmacokinetic properties (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 399-404 
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    ISSN: 1432-1041
    Keywords: Esmolol ; β1-Adrenoceptor antagonist ; tricresylphosphate ; pharmacokinetics ; effect kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of esmolol at different rates of infusion (100, 250 and 500 μg·kg−1 BW·min−1) were compared with β-adrenoceptor occupancy (β1 and β2, estimated by a subtype selective radioreceptor assay) and plasma concentrations of esmolol and its acid metabolite were measured by HPLC. Up to a rate of infusion of esmolol of 500 μg·kg−1 BW·min−1 there was a maximal β1-receptor occupancy of 84.7% while β2-receptor occupancy was below the detection limit; confirming the β1 selectivity of esmolol. Exercise-induced increases in heart rate and systolic blood pressure were reduced by esmolol in a dose-dependent manner. The estimated EC50 values of rate of infusion for the reduction in heart rate and systolic blood pressure during exercise were 113 and 134 μg·kg−1 BW · min−1, respectively. Additionally, heart rate and systolic blood pressure were reduced moderately at rest. Because of the short elimination half-life of esmolol caused by the rapid hydrolysis to its acid metabolite, 45 min after end of infusion high plasma concentrations of the metabolite (maximally 80 μg·ml−1) but no esmolol were detectable. Since no in vivo effects have been observed, despite the presence of high plasma concentrations of the metabolite, the metabolite did not participate in the observed effects up to an infusion rate of esmolol of 500 μg·kg−1 BW·min−1. The plasma concentrations of antagonist detected by radioreceptor assay and plasma concentrations of esmolol detected by HPLC showed a good correlation (r=0.97). Since the cardiovascular effects, determined before and 45 min after termination of infusion of esmolol were similar, it can be concluded that the observed effects on heart rate and systolic blood pressure are exclusively mediated by esmolol.
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    Influence of age, frailty and liver function on the pharmacokinetics of brofaromine (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 387-391 
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    ISSN: 1432-1041
    Keywords: Key words Liver function tests; elderly ; pharmacokinetics ; geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h⋅l−1, clearance was reduced (5.0 vs. 11.8 l⋅h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P 〈 0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
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    Pharmacokinetics and pharmacodynamics of ramipril and piretanide administered alone and in combination (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 545-550 
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    ISSN: 1432-1041
    Keywords: Ramipril ; Piretanide ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers. The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0–4 h) and ramiprilat (0–24 h) (from 15.8 to 19.8 ng·ml−1·h, and from 63.4 to 74.6 ng·ml−1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide. The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril. Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers.
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    On the relation between standard deviation and arithmetic mean in pharmacokinetic studies (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 573-574 
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    ISSN: 1432-1041
    Keywords: Standard deviation ; Arithmetic mean ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00196120
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    Effect of saliva flow rate on saliva phenytoin concentrations: implications for therapeutic monitoring (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 565-567 
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    ISSN: 1432-1041
    Keywords: Phenytoin ; Saliva ; therapeutic drug monitoring ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of atropine-induced reductions in saliva flow rate on saliva phenytoin concentrations were evaluated in a randomised placebo-controlled crossover study in a group of epileptic patients stabilised on the drug. Pretreatment with atropine caused significant reductions in saliva flow rates during the first 4 h, compared to saline. The AUC0–4 h for saliva flow rate was significantly reduced by atropine (245 g vs 327 g) and the saliva phenytoin AUC0–4 h was significantly increased (5.6 μg · ml−1 · h vs 4.5 μg · ml−1 · h) without affecting plasma phenytoin concentrations. The saliva/plasma phenytoin AUC0–4 h ratio was therefore significantly increased by atropine (0.15 vs 0.12). However, there was a poor correlation between saliva/plasma phenytoin concentration ratios and saliva flow rates for the two treatments in the individual patients (correlation coefficient ranged from 0.25 to 0.65). These findings demonstrate that saliva phenytoin concentrations are increased by reductions in saliva flow rate. Caution is therefore required when saliva phenytoin concentrations are used for therapeutic monitoring in the presence of factors which may affect saliva flow rate.
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    Cyclosporine pharmacokinetics in nephrotic and kidney-transplanted children (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 61-65 
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    ISSN: 1432-1041
    Keywords: Cyclosporine A ; kidney transplant ; nephrotic syndrome ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetic parameters of cyclosporine (CsA) were determined in 23 kidney transplant recipients and 19 children with nephrotic syndrome, after intravenous and oral administration. The mean bioavailability was 39 %, blood clearance was 0.55 l · h-1 · kg-1 and volume of distribution at steady-stade was 2.77 l · kg-1. The absorption profile was monophasic (67 %), biphasic (29 %) or poor (4 %). The maximum blood concentration of CsA was significantly higher in children with a monophasic profile than in children with a biphasic profile (550 vs 380 ng · ml-1). Blood clearance was significantly higher in the transplant recipients than in the patients with nephrotic syndrome (0.65 vs 0.43 l · h-1 · kg-1. Although age, haematocrit, creatinine clearance, serum albumin and cholesterol differed between the two groups, only haematocrit and creatinine clearance were significantly (negatively) correlated with CsA clearance.
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    Differences in the bioavailability of dihydrotachysterol preparations (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 81-84 
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    ISSN: 1432-1041
    Keywords: Dihydrotachysterol ; bioavailability ; pharmacokinetics ; human ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability of four preparations containing dihydrotachysterol (DHT2) was tested in two separate trials with administration of single, oral doses of 1 mg per individual. The relative bioavailability of corresponding preparations (capsules vs capsules and oral solution vs oral solution) was tested in a randomised, crossover pattern within the same group of volunteers. Two different groups of 24 healthy volunteers took part in each trial. Solution and capsule bioavailability was also compared inter-individually. A new sensitive HPLC-method (quantification limit 0.5 ng · ml-1) was used for the measurement of DHT2 concentration in serum. Three of the preparations tested had a similar bioavailability (mean AUC values of 195.5–223 ng · h · ml-1); the bioavailability of the fourth preparation (A.T.10 oral solution) was considerably lower (mean AUC value 111.5 ng · h · ml-1). The present dosage recommendations of all four preparations are identical. A new dosage recommendation is thus required for the oral solution with low bioavailability (A.T.10).
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    Doxycycline carrageenate — an improved formulation providing more reliable absorption and plasma concentrations at high gastric pH than doxycycline monohydrate (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 143-146 
    Details
    ISSN: 1432-1041
    Keywords: Doxycycline ; bioavailability ; pH dependent absorption ; pharmacokinetics ; carrageenate ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of increased gastric pH (obtained by pre-treatment with omeprazole) on the bioavailability of doxycycline monohydrate and doxycycline carrageenate has been investigated in 24 healthy volunteers, using an open, randomised, four-treatment, four-period, crossover, 2×2 factorial design. Each subject received a single dose of 100 mg of each of the doxycycline formulations with and without pre-treatment with omeprazole (40 mg daily for 7 days). The two formulations were bioequivalent (rate and extent) during fasting without omeprazole pre-treatment, whereas after omeprazole, the monohydrate showed a highly significant decrease in bioavailability (38% for AUC and 45% for Cmax) compared to the carrageenate formulation, which was not affected by prior administration of omeprazole. Many of the subjects did not reach a therapeutic plasma level of doxycycline during the combination of omeprazole and doxycycline monohydrate, and most adverse events (mainly gastrointestinal) were reported after this combination. As large populations of patients have a high gastric pH due to frequent use of H2-blockers, proton pump inhibitors and antacids, as well as to physiological achlorhydria, the decreased absorption of doxycycline monohydrate may well have a clinical impact, for example when the patients are treated with tetracyclines for an infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199878
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    The pharmacokinetics and pharmacodynamics of medifoxamine after oral administration in healthy elderly volunteers (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 163-166 
    Details
    ISSN: 1432-1041
    Keywords: Medifoxamine ; pharmacokinetics ; pharmacodynamics ; elderly volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and psychomotor effects of medifoxamine, a 5 HT reuptake inhibitory antidepressant, were studied in healthy elderly volunteers after single and multiple dosing. The elimination half life (t1/2z) after single doses of 300 mg was 2.8 h — almost identical to that found in young volunteers. After seven days of dosing at 100 mg three times daily the mean corrected AUC after 300 mg significantly increased from 1.04 to 1.34 mg.h.l−1 and t1/2z increased to 4.0 h (NS). There were no significant changes in critical flicker fusion frequency, symbol digit substitution, continuous attention or choice reaction times.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199882
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    Pharmacokinetics and dosage recommendations of teicoplanin in patients treated by continuous veno-venous haemodialysis (CVVHD) (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 179-180 
    Details
    ISSN: 1432-1041
    Keywords: Teicoplanin ; haemodialysis ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199886
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    Receptor binding assays in analysing the bioavailability and pharmacodynamic bioequivalence of active drug moieties (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 237-242 
    Details
    ISSN: 1432-1041
    Keywords: Metoprolol ; bioavailability ; bioequivalence ; receptor binding assay ; pharmacokinetics ; sustained release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability and pharmacodynamic bioequivalence of a conventional and an experimental sustained-release formulation of 100 mg metoprolol tartrate were studied in a randomised cross-over study in seven healthy volunteers by assessing over 24 h the plasma kinetics of R,S-metoprolol, its β1-adrenoceptor binding component, and by determining the extent to which the active drug moiety in plasma occupied rabbit lung β1-and rat reticulocyte β2-adrenoceptors. The formulations differed markedly in their kinetic characteristics: the peak plasma concentration (Cmax) of R,S-metoprolol after administration of the conventional formulation was 140 ng·ml−1, (n=7) and it was approximately one-third of that after the sustained-release formulation, 49 ng·ml−1, (n=6); the AUC0–24 h-values for the formulations were 700 and 310 ng·h·ml−1, respectively. The Cmax for the β1-adrenoceptor binding component of metoprolol was 180 ng·ml−1 (n=7) after administration of the conventional, and 74 ng·ml−1 after administration of the sustained-release formulation. The corresponding AUC0–24 h-values for the receptor binding component were 920 and 470 ng·h·ml−1 (n=7). Thus, the kinetic differences between R,S-metoprolol and the β1-receptor binding component were considerable and they were affected by the type of formulation. In general, after administration of the sustained-release formulation, the percentage β1- and β2-adrenoceptor occupancy of metoprolol in plasma was 5–15% less than after administration of the conventional formulation. At 0.5–1.5 h after drug intake the average β1-adrenoceptor occupancy of the conventional formulation varied between 80–90% and that of the sustained release formulation between 20–76%. At these times the differences in receptor occupancy were significant; at 0.5–2 h after drug intake the average β2-adrenoceptor occupancy of the conventional formulation varied from 20–30%, and that of the sustained-release formulation was 2–17%. At other times the difference in receptor occupancy between the formulations was not significant. The results demonstrate that plasma concentration-kinetics were more discriminating than β-adrenoceptor-binding in analysing bioequivalence. It was possible to determine the bioavailability of the active ingredient of metoprolol and to study pharmacodynamic bioequivalence by using receptor binding assays.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00192555
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    Methotrexate in juvenile rheumatoid arthritis (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 507-511 
    Details
    ISSN: 1432-1041
    Keywords: Methotrexate ; Juvenile rheumatoid arthritis ; pharmacokinetics ; age dependence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Children with juvenile rheumatoid arthritis (JRA) have been reported to require higher doses (per kg body weight) of methotrexate (MTX) than adults with rheumatoid arthritis to control their disease. The purpose of the present study was to characterise the plasma pharmacokinetics of MTX and its major metabolite, 7-hydroxymethotrexate (7-OHMTX) in children, and to compare the results with those previously obtained in adults. Thirteen patients (age 5–16 y) with JRA (median disease duration 5.5 y) were studied after once weekly oral administration of MTX (median 0.21 mg·kg−1). The analytical method was sufficiently sensitive to permit determination of plasma and urinary concentrations of MTX and 7-OHMTX during the entire dose interval in most of the patients. The dose normalized area under the plasma concentration versus time-curve (AUC) of MTX increased with the age of the children and was lower than previously found in adults. The dose normalized AUC of 7-OHMTX was not dependent on age. No correlation was found between the AUCs of MTX and 7-OHMTX. The results suggest that the age-dependence of the pharmacokinetics of MTX might explain the observation that at least some children require higher doses of MTX than adults to obtain a sufficient therapeutic effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193703
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    Antipyrine disposition in obesity: evidence for negligible effect of obesity on hepatic oxidative metabolism (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 525-530 
    Details
    ISSN: 1432-1041
    Keywords: Antipyrine disposition ; Obesity ; pharmacokinetics ; oxidative metabolism ; weight reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Following an overnight fast and 2 days of abstention from caffeine, a single 1.0-g oral dose of antipyrine was administered to 20 obese but otherwise healthy subjects (group A) and 11 healthy volunteers (group B). Weight, Body Mass Index (BMI) and % of Ideal Body Weight (IBW) were significantly greater in the obese than in the lean group. (Mean 110.4 vs 62.7 kg; 38.5 vs 22.3 kg · m−2 and 181vs 106 % respectively). In a subgroup of 6 obese subjects (group C) antipyrine was given again 11.3 months later after a 29.8 kg mean weight loss. Antipyrine apparent volume of distribution (V) and elimination half-life (t 1/2) were significantly greater in the obese than in the lean group (V 49.9 vs 34.3 l respectively; t 1/2 15.5 vs 12.0 h respectively), but its clearance rate (CLo) values were similar. V corrected for total body weight was significantly reduced in group A than in group B (0.45 vs 0.55 l · kg−1 respectively). Stratified comparison of antipyrine pharmacokinetics between obese and lean subjects according to age, gender and smoking habits did not alter the overall results. In group C, weight reduction was associated with a significant decrease in antipyrine V (from 51.8 to 47.5 l) and t 1/2 (from 15.1 to 12.7 h), and a non-significant increase in antipyrine CLo. We conclude that in severely obese subjects, antipyrine total V is mildly increased but V corrected for total body weight is significantly decreased. In addition, obesity is associated with a slight prolongation of antipyrine t 1/2 whereas its CLo is unaltered. These findings may indicate that obesity, even in its extreme form, has a negligible effect on the oxidative metabolic capacity of the liver.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193706
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    Oral bioavailability of CHF1194, an inclusion complex of piroxicam and β-cyclodextrin, in healthy subjects under single dose and steady-state conditions (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 531-536 
    Details
    ISSN: 1432-1041
    Keywords: Piroxicam ; β-Cyclodextrin ; pharmacokinetics ; healthy volunteers ; multiple dose ; adverse event
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract CHF1194 is an inclusion complex of β-cyclodextrin with the nonsteroidal anti-inflammatory drug piroxicam. In man, β-cyclodextrin acts as a carrier of piroxicam. As the inclusion complex of piroxicam-β-cyclodextrin is wettable and more water soluble, the absorption rate of the drug is increased whilst its other pharmacokinetic characteristics remain unchanged. The aim of the present study in 12 healthy subjects was to compare the oral bioavailability of 20 mg piroxicam in a CHF1194 tablet and a plain piroxicam capsule after a single dose and after two weeks of once daily administration, and also to assess the plasma levels and urinary excretion of β-cyclodextrin after CHF1194 administration. The two treatments were administered in cross-over fashion, separated by a wash-out period of three weeks. Piroxicam, 5′-hydroxypiroxicam and β-cyclodextrin were monitored in plasma and urine for 120 h after the first and last doses. Clinical tolerance was excellent and no adverse event occurred during either phase of the study. The extent of absorption of piroxicam from the CHF1194 tablet after the single dose was equivalent to that after the plain piroxicam capsule, within confidence limits of less than 80–125%. After repeated dosing, CHF1194 yielded the same steady-state systemic concentrations of piroxicam and 5′-hydroxypiroxicam as the reference capsule, and similar excretion pattern of the metabolite. After both single and multiple dosing, piroxicam was absorbed more rapidly after CHF1194, an expected consequence of the complexation of piroxicam with β-cyclodextrin. This may be of therapeutic interest as it might accelerate the onset of pain relief. The pharmacokinetics of piroxicam was linear after the doses used here, suggesting that long term treatment with CHF1194 should not require any change in dosing regimen. Even after 14 days of repeated administration of CHF1194, β-cyclodextrin could not be detected in plasma or urine, suggesting that in man the unchanged oligosaccharide was absorbed to a very small extent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193707
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    Changes in clearance create pharmacokinetic pitfalls as illustrated by studies on tiopronin (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 575-575 
    Details
    ISSN: 1432-1041
    Keywords: Renal clearance ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196121
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  • 98
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    Conventional and controlled release diltiazem (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 75-79 
    Details
    ISSN: 1432-1041
    Keywords: Diltiazem ; Angina pectoris ; controlled release formulation ; metoprolol ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Diltiazem CR tablets 120 mg b.i.d. for 1 week were compared with plain tablets 60 mg q.i.d. in 13 healthy male volunteers in a study of pharmcokinetic variables. Their antianginal efficacy was also compared in 23 patients with stable angina pectoris who were already on metoprolol. Both studies were of randomised, cross over design, and the clinical study was double blind. The pharmacokinetic variables of the two formulations were very similar except for the longer tmax of 4.4 h for diltiazem CR in comparison to 2.9 h for the plain tablets. The mean relative bioavailability of diltiazem CR in comparison with plain tablets was 1.14. The clinical study showed that after four weeks on diltiazem CR 120 mg b.i.d. or diltiazem plain tablets 60 mg q.i.d. in addition to metoprolol, there were significant decreases in weekly anginal attacks from 11 to 5 attacks/week, the number of nitroglycerin tablets consumed from 6 to 3 tablets/week, and an increase in the maximum workload from 116 to 126 and 123 W for diltiazem CR and plain diltiazem tablets, respectively, as compared to placebo. Five of the patients were angina free during diltiazem treatment. No difference in antianginal efficacy between the two preparations was seen. It was concluded that CR 120 mg b.i.d. appears bioequivalent to plain diltiazem tablets 60 mg q.i.d.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193483
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  • 99
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    The effect of renal impairment on the pharmacokinetics of oxcarbazepine and its metabolites (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 161-167 
    Details
    ISSN: 1432-1041
    Keywords: Oxcarbazepine ; 10,11-dihydro-10-hydroxy-carbamazepine ; renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the effect of renal impairment on the pharmacokinetics of oxcarbazepine, its active monohydroxy-metabolite (which predominates in plasma), their glucuronides, and the inactive dihydroxy-metabolite after a single oral dose of oxcarbazepine (300 mg). Six subjects with normal renal function and 20 patients with various degrees of renal impairment participated. The mean areas under the plasma concentration-time curves of oxcarbazepine and its monohydroxy-metabolite were 2–2.5-times higher in patients with severe renal impairment (CLCR〈10 ml·min−1) than in healthy subjects. The apparent elimination half-life of the monohydroxy-metabolite [19 (SD 3) h] in these patients was about twice that in healthy subjects. The effect of renal impairment on the plasma concentrations of glucuronides was more marked. The renal clearances of the unconjugated monohydroxy-metabolite and its glucuronides (the main compounds recovered in urine) correlated well with creatinine clearance. The maximum target dose in patients with slight renal impairment (CLCR〉30 ml·min−1) should not be changed. In patients with moderate renal impairment (CLCR10–30 ml·min−1) it should be reduced by 50%. In patients with severe renal impairment (CLCR〈10 ml·min−1), the glucuronides of oxcarbazepine and its monohydroxy-metabolite are likely to accumulate during repeated administration, and dosage adjustment of oxcarbazepine in these patients could not be proposed from this single administration study.
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    URL: http://dx.doi.org/10.1007/BF00194967
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  • 100
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    Furosemide disposition in patients on CAPD (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 385-390 
    Details
    ISSN: 1432-1041
    Keywords: Furosemide ; Dialysis ; continuous ambulatory peritoneal ; drug disposition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Single doses of oral and intravenous furosemide were given to 8 healthy male volunteers (40 mg) and 11 patients with renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD) (80 mg). In the volunteers, absorption was variable. Only one half of the intravenous dose and one third of the oral dose was available for renal pharmacological action as judged by the urinary recovery. In the patients, absorption was also variable and was markedly delayed (t max 128 vs 90 min) but more complete (bioavailability 70.1 vs 53.6%). The differences between the two groups were not significant, however (95% C.I.: -90 to 30 and -40.4 to 7.5 respectively). The mean elimination half-life was significantly longer in the patients following both the oral (228 vs 65.1 min) and intravenous dose (195 vs 60.3 min). The total body clearance of furosemide in the volunteers was 138 ml·min−1 and this was much lower in the CAPD patients (61.9 ml·min−1) in whom the renal clearance was minimal. The peritoneal clearance of furosemide was negligible. Although there were trends indicating differences in absorption between the two groups, the significant differences in furosemide disposition observed in CAPD patients were due to renal failure.
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    URL: http://dx.doi.org/10.1007/BF00194955
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