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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 714 (1994), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: transdermal administration ; microcirculation ; morphine ; dextrans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a clinical alternative to drug administration by injection or infusion. Methods. A simple, mechanical device (Cellpatch) enables both the formation of a standardized small epidermal bleb and exposure of the circular base of the bleb to drug. The epidermis is split off by suctioning without bleeding or discomfort in a layer superficial to dermal capillaries and nociceptor nerves. Transdermal invasivity is thus avoided. Absorption of dextran test drug in aqueous solution vs molecular weight (3 kDa–70 kDa) and erosion area (3 kDa, diameter: 3–10 mm) were studied in healthy volunteers. The feasibility of using Morphine cell-patch (cell filled with 20 mg/ml morphine hydrochloride, aqueous solution, erosion diameter 6 mm) for post-operative pain relief was studied in two different patient groups; the Cellpatch was removed after 48 hours. Plasma morphine concentrations were determined at intervals. Results. Dextrans of all sizes were efficiently absorbed transdermally, although absorption decreased with increasing molecular weight. The degree of absorption was directly related to the area of the mini-erosion. There were no sign of dose-dumping even with the largest erosions. The Cellpatch performed well in the demanding conditions of the postoperative unit, and was considered easy to use. Pharmacokinetically, the postoperative morphine delivery was related to that of a continuous infusion, with variability and dose in the same range as a continuous morphine infusion used clinically for providing basal pain relief. There were no bacterial growth in the morphine cells at 48 h. Reepithelialization of the erosion was rapid. Conclusions. The feasibility of administering drugs in a wide size range by passive diffusion through a standardized skin mini-erosion was demonstrated; the rate of absorption decreased with increasing molecular weight. The small area of the erosion restricts and controls the concentration driven diffusion of drug into the circulation. As a consequence of the favorable findings, three placebo-controlled clinical studies using Morphine cellpatch for postoperative pain relief are currently underway.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-904X
    Keywords: absorption ; intestine ; pancreatic juice ; peptides ; pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The present investigation was done to study the intestinal absorption of three oxytocin peptide analogues and to elucidate the role of pancreatic juice on their absorption. Methods. In conscious chronically catheterized pigs (6–8 weeks of age) plasma concentration of the peptides, [Mpa1, D-Tyr(Ethyl)2, Thr4, Orn8]-oxytocin (F314), [Mpa1, D-Tyr(Ethyl)2, Val4, D-Arg8]-oxytocin (CAT), and [Mpa1, D-Tyr(Ethyl)2, Thr4, Orn8, desGly9, carba6]-oxytocin (F327) after intraduodenal administration, during presence or diversion of the pancreatic juice via a pancreatic duct catheter, were determined by radioimmunoassay. The stability of the peptides to degradation was determined in vitro by incubation with activated pancreatic juice, chymotrypsin or trypsin, followed by reversed phase HPLC analyses. Results. All peptides were absorbed with a bioavailability of about 0.5% in the presence of pancreatic juice, but increased to 1.0%, 2.1%, and 13.5% for F314, CAT, and F327, respectively, when the pancreatic juice was diverted from the intestine. After incubation with pancreatic juice 95% of F314, 98% of F327, and 100% of CAT was found intact. When incubated with trypsin CAT remained intact while F314 and F327 were degraded by 54% and 46%, respectively. Incubation with purified chymotrypsin did not degrade the test peptides. Conclusions. The results indicate that the increased absorption of peptides observed under conditions of diverted pancreatic juice cannot only be explained by the absence of pancreatic enzymes, but also by changed absorptive properties in the gastrointestinal tract.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-904X
    Keywords: peptides ; drug administration ; skin ; absorption ; oxytocin ; vasopressin ; drug absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Transdermal administration of the peptides [Mpa1, D-Tyr (Ethyl)2, Thr4, Orn8]-oxytocin (antocin) and [Mpa1, D-Arg8]-vasopressin (dDAVP) was studied in healthy volunteers. Methods. A standardized skin erosion was formed preliminary by suctioning. The peptides were administered in plastic reservoirs through a 5 mm erosion and the absorption was followed for a six-day period with plasma concentration determinations on days 1, 3 and 6 with refilling the reservoirs daily with 15 µm and 10 mM solutions of dDAVP and antocin, respectively. Fourteen healthy non-smoking volunteers divided equally between the sexes, participated in the study. Plasma concentrations were measured using specific radioimmunoassays. Reservoir concentrations and metabolic stability of the peptides were determined using reverse-phase HPLC. Results. Both antocin and dDAVP were absorbed across the skin erosion. The absorption pattern was biphasic with a high initial absorption during days 1 and 2 followed by a lower absorption on days 3 and 6. The absorption on day 1, which was estimated at more than 50% for both peptides during a 24 h period, corresponded to a simultaneous decrease in peptide concentration in the reservoirs. The extent of absorption for antocin on days 3 and 6 was 1/3 to 1/6, respectively, of that observed on day 1. Antocin was minimally degraded in the skin reservoir while dDAVP was intact. However, accumulation of cellular material appeared in the antocin reservoirs. The absorption of antocin was reduced by exposure to intact skin surrounding the skin erosion. No pain was experienced and no scar formation was observed. Conclusions. The observed biphasic absorption may be a consequence of the mild inflammatory response occurring subsequent to eroding the skin. The standardized skin erosion may provide a route for the short-term delivery of otherwise poorly absorbable peptide and protein drugs.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of clinical monitoring and computing 14 (1998), S. 425-431 
    ISSN: 1573-2614
    Keywords: Gas density ; helium ; oxygen ; venturimeter ; measurement ; tidal volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Medicine
    Notes: Abstract Objective. Mixtures of helium and oxygen are regaining a place in the treatment of obstruction of the upper and lower respiratory tract. The parenchymal changes during the course of IRDS or ARDS may also benefit from the reintroduction of helium/oxygen. In order to monitor and document the effect of low-density gas mixtures, we evaluated the Datex AS/3 Side Stream Spirometry module with D-lite® (Datex-Engstrom Instrumentarium Corporation, Finland) against two golden standards. Methods. Under conditions simulating controlled and spontaneous ventilation with gas mixtures of He (approx. 80, 50, and 20%)/O2 or N2 (approx. 21 and 79%)/O2, simultaneous measurements using Biotek Ventilator Tester (Bio-Tek Instr., Vermont, USA) or body plethysmograph (SensorMedics System, Anaheim, USA) were correlated with data from the spirometry module. Data were analyzed according to a statistical regression model resulting in a best-fit equation based on density, voltage, and volume measurements. Results. As expected, the D-lite (a modified Pitot tube) showed density-dependent behaviour. Regression equations and percentage deviation of estimated versus measured values were calculated. Conclusion. Measurements with the D-lite using low-density gases are satisfactorily contained in best-fit equations with a standard deviation of less than 5% during all ventilatory modes and mixtures.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 513-529 
    ISSN: 1573-8744
    Keywords: desmopressin ; indirect-response modeling ; overhydration ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The objective of the present study was to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of desmopressin in healthy male subjects at different levels of overhydration. Also, we examined if an indirect-response model could be related to renal physiology and the pharmacological action of desmopressin. Eight healthy male subjects participated in this open, randomized crossover study with three periods. Each subject was orally water loaded (0 to 20ml·kg −1 body weight) on 3 study days in order to achieve three different levels of hydration. After the initial water load, urine was voided every 15 min and the volumes were measured. To ensure continuous overhydration the subjects replaced their fluid loss with drinking-water. When a steady-state diuresis was achieved after approximately 2 hr, 0.396 μg of desmopressin was administered intravenously as a bolus injection. Blood was sampled and urine was collected at intervals throughout the study day (10 hr). An indirect-response model, where desmopressin was assumed to inhibit the elimination of response, was fit to the urine osmolarity data. There were no statistically significant effects of different levels of hydration, as expressed by urine flow rate at baseline, on the estimates of the PK and PD model parameters. The calculated terminal half-lives of elimination (t1/2 β) ranged between 2.76 and 8.37 hr with an overall mean of 4.36 hr. The overall means of plasma clearance and the volumes of distribution of the central compartment (Vc ) and at steady state (Vss ) were estimated to be 1.34 (SD 0.35) ml·min −1 ·kg −1 , 151 (SD28) ml·kg −1 , and 386 (SD 63) ml·kg −1 , respectively. High urine flow rate, indicating overhydration, produced a diluted urine and thus a low osmolarity at baseline (R0 ). The effect of the urine flow rate on the urine osmolarity at baseline was highly significant (p〈0.0001). The mean values for IC50 and the sigmoidicity factor (γ) were 3.7 (SD 1.2) pg·ml −1 and 13.0 (SD 3.5), respectively. In most cases when there was a high urine flow rate at baseline, the model and the estimated PD parameters could be related to the pharmacological action of desmopressin and renal physiology. Thus, the indirect-response model used in this study offers a mechanistic approach of modeling the effect of desmopressin in overhydrated subjects.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-904X
    Keywords: oxytocin ; vasopressin ; rat ; in vitro ; intestine ; peptide absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The transmural intestinal passage of some oxytocin and vasopressin analogues (oxytocin, OT; [Mpa1, D-Arg8]vasopressin, dDAVP; [Mpa1, Tyr (OMe)2, carba6]oxytocin, carbetocin; [Mpa1, D-Tyr (OEt)2, Thr4, Orn8]vasotocin, antocin II; [Mpa1, D-Tyr (OEt)2, Thr4, desPro7Orn8Gly9NH2]tocinoic acid-NH(CH2)3NH2, desPOG-antocin II-NH(CH2)3NH2) was studied using isolated proximal and distal segments in the rat. All peptides (measured as peptide-like immunoreactivity) displayed a higher transport rate across distal intestinal segments as determined by radioimmunoassay (RIA). The smallest peptide, des POG-antocin II-NH(CH2)3NH2, was transported at the fastest rate. No correlation of lipophilicity with transport rate was observed. Determination of the amount of peptide remaining in the mucosal media at the end of the incubation period by HPLC did not reveal any visible degradation products. However, the large difference in transport rate between [3H]OT and immuno-reactive OT indicates mucosal metabolism of this peptide. [3H]d-DAVP was distributed in a larger mucosal volume than the extracellular space marker [3H]inulin, indicating tissue uptake, but was too low (〈100% of buffer concentration) to make an active transport mechanism likely. The differences in peptide transport rates between proximal and distal intestinal segments are most likely due to a higher distal paracellular permeability despite a decreased absorptive surface area at this region.
    Type of Medium: Electronic Resource
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  • 8
    Publication Date: 2013-07-23
    Description: A previously reported diketopyrrolopyrrole (DPP)-phenyl copolymer is modified by adding methoxy or octyloxy side chains on the phenyl spacer. The influence of these alkoxy substitutions on the physical, opto-electronic properties, and photovoltaic performance were investigated. It was found that the altered physical properties correlated with an increase in chain flexibility. Well-defined oligomers were synthesized to verify the observed structure-property relationship. Surprisingly, methoxy substitution on the benzene spacer resulted in higher melting and crystallization temperatures in the synthesized oligomers. This trend is not observed in the polymers, where the improved interactions are most likely counteracted by the larger conformational possibilities in the polymer chain upon alkoxy substitution. The best photovoltaic performance was obtained for the parent polymer: fullerene blends whereas the modifications on the other two polymers result in reduced open-circuit voltage and varying current densities under similar processing conditions. The current densities could be related to different polymer: fullerene blend morphologies. These results show that supposed small structural alterations such as methoxy substitution already significantly altered the physical properties of the parent polymer and also that oligomers and polymers respond divergent to structural alterations made on a parent structure.
    Electronic ISSN: 1996-1944
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by MDPI Publishing
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  • 9
    Publication Date: 2005-01-01
    Print ISSN: 0273-1177
    Electronic ISSN: 1879-1948
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Published by Elsevier
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  • 10
    Publication Date: 2007-01-01
    Print ISSN: 0273-1177
    Electronic ISSN: 1879-1948
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Published by Elsevier
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