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  • Articles  (24)
  • pharmacokinetics  (24)
  • Springer  (24)
  • Wiley
  • 2020-2020
  • 1970-1974  (24)
  • 1945-1949
  • 1973  (18)
  • 1972  (6)
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  • Articles  (24)
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  • Springer  (24)
  • Wiley
Years
  • 2020-2020
  • 1970-1974  (24)
  • 1945-1949
Year
  • 1
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    Springer
    European journal of clinical pharmacology 5 (1972), S. 44-52 
    ISSN: 1432-1041
    Keywords: alprenolol ; serum drug level ; exercise ; man ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of alprenolol on heart rate and systolic blood pressure were studied in healthy subjects during standardized exercise on a bicycle ergometer. In one series of experiments, in which serum concentrations of alprenolol were also measured, the effects of single oral doses of 50, 100 and 200 mg of alprenolol and a placebo were compared by a double blind cross-over technique. In a second series of experiments 100 mg alprenolol was given four times in one day and the effect was followed for up to eighteen hours after the last dose. — Alprenolol diminished the expected increase in heart rate and systolic blood pressure during exercise. The reduction of exercise tachycardia in a given individual was linearly related to the logarithm of the dose or the serum concentration of alprenolol. The serum concentrations required for a given reduction of exercise tachycardia varied almost one hundred-fold amongst the subjects studied. The biological availability of alprenolol was dose-dependent, probably due to a limited capacity biotransformation of the drug before it entered the general circulation. After a single dose the serum level of alprenolol and its chronotropic effect diminished at a rate corresponding to an elimination half life of about two hours. This rate of elimination was consistent with that calculated from the results of the four dose study.
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  • 2
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    European journal of clinical pharmacology 5 (1973), S. 174-180 
    ISSN: 1432-1041
    Keywords: Tricyclic antidepressant ; nortriptyline ; metabolism ; urine ; pharmacokinetics ; twins ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary excretion of nortriptyline (NT) and five of its metabolites was studied by quantitative gas chromatography in 22 twins and 7 unrelated healthy subjects after single (1 mg/kg) and multiple oral doses (0.4 mg/kg t.i.d.) of NT hydrochloride. A mean recovery of 62% of the dose was found after both single and multiple doses. The metabolite pattern in the urine was qualitatively and quantitatively identical in the two regimes, but there were marked variations in the pattern of metabolites between individuals. The disappearance rate of NT from the plasma was mainly determined by the metabolism of NT to 10-hydroxynortriptyline, which varied considerably between individuals. The data suggest that in certain rapid NT metabolizers, the upper limit for the overall clearance of NT from the plasma (if extrahepatic metabolism is assumed to be negligible) might be set by the blood flow through the liver.
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  • 3
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    European journal of clinical pharmacology 6 (1973), S. 268-270 
    ISSN: 1432-1041
    Keywords: Diphenhydramine ; orphenadrine ; gas-liquid chromatography ; N-selective detector ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method is described for the assay of nanogram quantities of diphenhydramine and orphenadrine in human plasma. The procedure employs gas-liquid chromatography and a high sensitivity nitrogen detector. It has been used to assay diphenhydramine in plasma after oral administration of therapeutic doses.
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  • 4
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    European journal of clinical pharmacology 6 (1973), S. 234-238 
    ISSN: 1432-1041
    Keywords: Phenobarbital ; neonate ; maternal-fetal exchange ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of phenobarbital were measured in 18 newborn infants for one to two weeks after birth. The drug had been administered prenatally to the mothers as part of treatment for maternal hypertension or toxaemia. The plasma half-life of the drug in the infants (77–404 h) was inversely correlated with the extent of prenatal exposure to it. In three infants a bi-phasic plasma curve was found as there was a sudden change from slow to fast disappearance on the 5th to 7th day of life.
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  • 5
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    European journal of clinical pharmacology 6 (1973), S. 44-53 
    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; plasma clearance ; gas chromatography — mass spectrometry ; pharmacogenetics ; twins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five identical (monozygotic) and 6 fraternal (dizygotic) sets of healthy twins between 47 and 53 years of age were given a single oral dose of nortriptyline (NT) hydrochloride 1 mg/kg. The plasma half-life, the apparent volume of distribution, and the plasma clearance of NT were estimated for each subject as well as the urinary excretion rate of conjugated and unconjugated 10-hydroxynortriptyline (10-OH-NT). “Steady-state” plasma levels predicted from the reciprocal single dose plasma clearance rate of NT agreed well with those observed in a previous study of the same twins 2 years previously. In the present study, there was a 5-fold range of the plasma half-lives and 2-fold variation in the apparent volume of distribution of NT (assuming complete availability on oral administration). No correlation was found between the plasma half-life and the apparent volume of distribution. Analysis of variance showed that most of the variability between persons in plasma half-life, apparent volume of distribution and conjugation of 10-OH-NT was genetically determined. The plasma half-life and apparent volume of distribution may contribute independently to the total interindividual variability of the “steady-state” plasma level of NT.
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  • 6
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    European journal of clinical pharmacology 5 (1972), S. 58-61 
    ISSN: 1432-1041
    Keywords: Pralidoxime chloride ; pharmacokinetics ; anti-cholinesterase poisoning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dose of 1.0 g (10.0–14.0 mg/kg body weight) of pralidoxime mixed with various cholinolytics was given by i.m. injection to 29 healthy male subjects. A concentration of pralidoxime in blood of 4 µg/ml was reached after 5 to 10 min with all the mixtures and was maintained for about 1 to 2 h. The calculated half lives of pralidoxime in three groups of subjects were 62.2, 60.0 and 61.8 min., respectively. — The urinary excretions of pralidoxime during the first 4 h after the injections averaged 75.0, 79.6 and 69.6 per cent, respectively, of the total amount given. — The results are compared with published information about similar oximes.
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  • 7
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    European journal of clinical pharmacology 4 (1972), S. 233-240 
    ISSN: 1432-1041
    Keywords: Sulphamethoxazole ; trimethoprim ; pharmacokinetics ; uraemia ; sulphonamides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulphamethoxazole (SMZ) and trimethoprim (TMP) have been investigated in four healthy volunteers, 15 patients with stable chronic renal failure and 3 patients on regular dialysis. The dosage schedule was 400 mg of SMZ and 80 mg of TMP orally every 12 h. The plasma concentrations and urinary excretion have been analysed in terms of a one compartment open model, allowing for elimination by renal excretion and metabolic processes. — At equilibrium the plasma concentrations of unchanged sulphonamide showed no significant correlation with the degree of renal impairment. The accumulation of TMP increased slightly without affecting the concentration ratio of both agents in plasma. In contrast, increasing accumulation of metabolized SMZ was demonstrated in the presence of renal insufficiency. Indirect evidence indicates that rising metabolite levels under these circumstances may lead to a displacement of unchanged sulphonamide from protein binding sites. — The cumulative urinary excretion amounted to 82.4% of the dose of sulphonamide administered, which probably corresponds to the fraction of the compound absorbed. The urinary concentration of biologically active SMZ was slightly below the plasma level, especially in advanced renal failure, but it remained above the minimum inhibitory concentrations reported in the literature. The concentration of TMP in urine was considerably higher than in plasma, it decreased with loss of renal function as did active SMZ.
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  • 8
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    European journal of clinical pharmacology 4 (1972), S. 191-195 
    ISSN: 1432-1041
    Keywords: Amobarbital ; pentobarbital ; barbiturates ; gas chromatography ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Gas chromatographic methods are described for the assay of amobarbital and pentobarbital in 500 µl samples of plasma, in concentrations down to 250 ng/ml. After ether extraction at pH 5.5, the barbiturates are reextracted into an alkaline solution of trimethylanilinium hydroxide and are determined quantitatively by gas chromatography as their dimethylated derivatives. The method has been used successfully in volunteers receiving therapeutic doses of these bariturates.
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  • 9
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    European journal of clinical pharmacology 6 (1973), S. 181-186 
    ISSN: 1432-1041
    Keywords: Phenothiazines ; thioridazine ; serum levels ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The rate of absorption of thioridazine varied greatly in ten healthy volunteers who took 100 mg in the morning after an overnight fast. The peak level in blood was also variable and it was reached 1 1/4 to 4 h after dosing. Maximal concentrations in the blood varied widely from 0.13 µg/ml to 0.52 µg/ml. No relation was found between the weight or sex of the subjects and the pharmacokinetics of the drug. The serum half life of thioridazine in three healthy volunteers was 9, 10 and 10 h respectively. In a group of 22 patients receiving less than 5 mg/kg body weight a day, there was a strong correlation between the dose and the morning or evening concentration of thioridazine in the blood. A positive correlation was also observed between the age of the patient and the serum level in those who received doses of less than 5 mg/kg body weight.
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  • 10
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    European journal of clinical pharmacology 6 (1973), S. 88-92 
    ISSN: 1432-1041
    Keywords: Noradrenaline pools ; 7-3H-noradrenaline ; neuro-effector junction kinetics ; pharmacokinetics ; sympathoadrenergic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A two-compartment model of 73HNA distribution has been developed for studying sympatho-adrenergic activity in intact man. After infusion of 73HNA at constant speed in resting normal subjects, the decay curves of the plasma concentration and urinary excretion of 73HNA were plotted against time. Analysis of the curves yielded constants and indirect indications about noradrenaline exchange processes in the extracellular environment. Complete evaluation of the neuronal pools and of the pathways of biosynthesis and metabolism was impossible, but it seemed likely that 73HNA entered small neuronal pools that underwent rapid exchange with the extracellular environment, a point of some interest in clinical and pharmacologic investigations.
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  • 11
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    European journal of clinical pharmacology 6 (1973), S. 137-140 
    ISSN: 1432-1041
    Keywords: Urography ; Hypaque® ; Urovist® ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Comparative tests were carried out, using a radioactive tracer method, on the pharmacokinetics of sodium and methylglucamine diatrizoate. A biological model was simulated using an analogue computer; and the rate and elimination constants, the elimination half life, and the ratio of tissue entry to tissue elimination constants were calculated. Over the period of time required for X-ray diagnosis, the two salts of the contrast medium acid which were tested did not alter the pharmacokinetics of the contrast medium itself.
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  • 12
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    European journal of clinical pharmacology 6 (1973), S. 245-250 
    ISSN: 1432-1041
    Keywords: Procaine amide ; N-acetylprocaine amide ; sustained-release ; pharmacokinetics ; ventricular arrhythmia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients with acute myocardial infarction were studied during treatment with either a conventional or a new sustained-release preparation of procaine amide in order to compare fluctuations in plasma concentration and urinary excretion of the drug during “steady state” conditions. Procaine amide in plasma was measured by spectrofluorimetry and the urine concentration of it and its major metabolite, N-acetylprocaine amide, by gas chromatography. The average fluctuation of plasma concentrations was 3.5±0.1 µg/ml during treatment with sustained-release tablets (dosage interval 8 h) and 4.2±0.4 µg/ml during treatment with ordinary tablets (dosage interval 4 h), i. e. it was 20% greater during treatment with the conventional preparation. There was no difference between the two preparations in recovery of the drug from urine (sustained-release tablets 85.4±3.0%; and conventional tablets 90.3±5.4%). Thus, the new sustained-release preparation of procaine amide administered 3 times daily produced the same range of plasma levels as the identical dose of conventional tablets given 6 times a day.
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  • 13
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    European journal of clinical pharmacology 6 (1973), S. 261-267 
    ISSN: 1432-1041
    Keywords: Alclofenac ; antiphlogistic ; man ; pharmacokinetics ; dosage regimes ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A one compartment open model has been found to fit plasma concentration data previously obtained in man after single oral doses of alclofenac; the parameters of the model are: $${\text{t}}_{\tfrac{{\text{1}}}{{\text{2}}}} $$ abs=1.3±0.7h, $${\text{t}}_{\tfrac{{\text{1}}}{{\text{2}}}} $$ el=3.5±1.2h, Vd/F=17±6. The model has been used successfully to predict steady-state plasma levels of alclofenac after multiple oral doses. One treatment schedule (initial dose 500 mg, maintenance dose 250 mg five times a day) was administered to two volunteers for five days and the plasma levels of alclofenac determined daily. The latter were in good agreement with computer predictions based on the model. It is now possible, therefore, to select the most suitable dosage regimes for this drug.
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  • 14
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    European journal of clinical pharmacology 4 (1972), S. 137-141 
    ISSN: 1432-1041
    Keywords: Fentanyl ; pharmacokinetics ; neuroleptanalgesia ; analogue computer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and urinary excretion of3H-fentanyl were studied in 5 human subjects after intravenous injection of this drug. After an initial rapid decline, the plasma level of fentanyl decreased slowly and approximately exponentially. The plasma concentration of metabolites remained almost steady from 1–3 h after injection. More than 60% of the administered radioactivity was excreted through the kidneys within 4 days. Only a small proportion of it was unchanged fentanyl. The rates of fall of plasma concentration and of urinary excretion were slower in man than in rabbits. — The time courses of plasma concentrations and of urinary excretion were simulated on an analogue computer. The results support the assumption that the different time courses of concentrations in man and rabbits are caused by slower metabolism in man. It seems likely that redistribution plays a dominant part in the short duration of action of fentanyl in man.
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  • 15
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    European journal of clinical pharmacology 4 (1972), S. 150-157 
    ISSN: 1432-1041
    Keywords: Antibiotics ; pharmacokinetics ; microbiological assay ; drug control ; neonatal septicaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The various steps of a paper disc micromethod for quantitative determination of plasma concentrations of antibiotics is described. Only 10 µl of plasma is needed for a single determination, allowing easy and repeated capillary sampling. Separate assay was attempted of three antibiotics in a mixture (streptomycin, cloxacillin and ampicillin), both by use of selective inhibitors (semicarbazide, penicillinase) in the culture medium and by choosing suitable strains of bacteria. In this way, it was possible to determine streptomycin and cloxacillin separately when all three antibiotics were present simultaneously in the plasma. The assay of ampicillin, however, was always influenced by the presence of even small concentrations of cloxacillin. The 95% confidence intervals of the standard curves for the three antibiotics are presented. — The method is suitable both for pharmacokinetic studies and for routine clinical control of plasma antibiotic levels, even in premature children.
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  • 16
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 51-68 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; cancer chemotherapy ; cell kinetics ; mathematical model ; cell cycle specific drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Predictive models have been developed to simulate cancer cell populations under treatment with cytotoxic drugs, with both direct-acting and cell cycle specific drugs being considered. Models of cell growth kinetics have been combined with simple pharmacokinetic models to complete the cell-drug interaction system. The models depend on knowing the distribution of generation time in the cell population, the cell-drug interaction, and the local concentration of the drug at the effective site. All of the quantities can be obtained, in principle, from separate experiments and combined to form a model describing several aspects of the cell-drug response system.
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  • 17
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 497-520 
    ISSN: 1573-8744
    Keywords: tissue distribution ; plasma protein binding ; tissue protein binding ; fat/water partition coefficient ; volumes of distribution ; corticosterone ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The concentration of a drug at its site of action will be affected by the ability of the drug to distribute to and pass through various membranes and tissues. Mechanisms of drug distribution are summarized in this paper and include the differences between intracellular and extracellular pH,active transport systems for drugs, distribution of drugs between fat and water in adipose tissues, the reversible binding of drugs to phospholipids and to various macromolecules including proteins, nucleic acid, and melanin. These mechanisms usually tend to decrease the concentration of unbound drugs at their sites of action, but usually not to the extent one would predict on the basis of in vitrobinding studies. The effects of drug distribution in altering the biological half-lives of drugs in the body are discussed as well as the interrelationship between the kinetic volumes of distribution for drugs and blood flow rates through the organs that eliminate these drugs. These concepts are illustrated for corticosterone levels following intravenous bolus injections and infusions into rats.
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  • 18
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 341-361 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacokinetic models ; bioavailability ; clinical metabolic profile ; chronic dosing regimens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The present status of pharmacokinetics is reviewed. Pharmacokinetic models and the basic concepts involved in applying models to blood, urine, bile, and tissue levels of drugs and metabolites are discussed. An outline of methods for pharmacokinetic analyses is proposed. Special emphasis is given to the determination of bioavailability of a drug from various dosage forms. Uses of pharmaco-kinetics in determining sites of drug action and in determining a clinical metabolic profile are suggested. The perturbations of magnitudes of pharmacokinetic parameters among individuals challenged with the drug can be used as a diagnostic tool in evaluating the state of dynamic processes, the presence of metabolic diseases and genetic abnormalities, and the failure of physiological functions. The use of pharmacokinetics and the prediction of chronic dosing regimens are reviewed. Typical curves depicting predicted blood levels on repetitive dosing are presented.
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  • 19
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 521-540 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; polygenically controlled disease states ; pharmacokinetic twin studies ; pharmacokinetic heritability ; ethanol ; antipyrine ; phenylbutazone ; bishydroxycoumarin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The application of pharmacokinetics to the elucidation of polygenic factors involved in drug disposition is discussed in the context of three questions: (a)How extensive is the variation among individuals in rate of plasma clearance for commonly used drugs? (b)If appreciable variation occurs, what are the relative contributions of genetic and environmental factors to its maintenance? (c) What role is played by polygenic factors in maintaining this variation?Large variance in plasma decay rates for phenylbutazone, ethyl biscoumacetate, antipyrine, isoniazid, and nortriptyline is noted throughout the general population. However, these large variations appear to be controlled predominately by genetic rather than by environmental factors on the basis of studies run on identical and fraternal twins. At the present time, an individual's capacity to metabolize drugs and the effects of various conditions in altering that basal, genetically determined capacity seem to be best indicated by measurements of the plasma antipyrine half-life. While the theoretical advantages of obtaining blood concentrations of drugs as a guide to their more rational administration are evident, several practical problems are discussed in this paper.
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  • 20
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 137-163 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; nonlinear regression ; drug distribution ; compartmental models ; computer program ; BASIC ; time sharing ; spectinomycin ; naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract COMPT, a computer program for optimizing the solution of integral compartmental models of drug distribution by nonlinear regression analysis, is written in extended BASIC for use in time-sharing computer systems. It is based on Hartley's modification of the Gauss-Newton gradient method. The characteristics and features of the program are indicated, and the program source listing is presented. This version of COMPT is designed to solve the two-compartment open model of intravenous drug administration. Examples of the results of the operational program are presented. The program is modifiable to permit analytical solutions for other types of systems described by nonlinear equations.
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  • 21
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 175-200 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; cancer chemotherapy ; pharmacodynamics ; cell kinetics ; vincristine ; vinblastine ; arabinosylcytosine ; cyclophosphamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A pharmacodynamic model is proposed and equations are developed for the quantitative analysis of dose-time-cell-survival curves produced by the administration of cell-cycle-specific chemo-therapeutic agents. The essential feature of the model is an irreversible, bimolecular mechanism of drug-receptor interaction which serves as the interface between the pharmacokinetics of the drug and the cell-cycle-cell-proliferation kinetics of the normal and neoplastic cells. A preliminary cell system which allows adequate characterization of the experimental data is a two-compartment model where cells are assumed to exist in their proliferative and nonproliferative phases. The chemotherapeutic model was used to analyze dose-time-cell-survival curves found in the literature for the effects of vincristine, vinblastine, arabinosylcytosine, and cyclophosphamide on lymphoma and hematopoietic cells in the mouse femur. Similarity in the values of the “cell-kill” constants for these drugs on the two cell types indicates that, in the cell systems studied, the proliferative state of the cells is the primary in vivodeterminant of selective chemotherapy.
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  • 22
    ISSN: 1573-8744
    Keywords: absorption ; amphetamine ; bioavailability ; elimination ; pharmacokinetics ; phentermine ; resin-bound drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Plasma levels of amphetamine and phentermine have been measured in man in a crossover study of the pharmacokinetics of these agents following oral administration of resin-bound and soluble salt formulations. The one-compartment open model with first-order drug absorption was fitted to the data from each subject by nonlinear regression methods and provided an excellent fit. Relative bioavailability of the two salts did not differ for either drug. In both cases the rate constant for absorption was significantly lower and less variable for the resinated compound.
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  • 23
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 295-305 
    ISSN: 1573-8744
    Keywords: diazoxide ; pharmacokinetics ; stable-isotope dilution ; GC-mass fragmentography ; solubility ; excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A specific, sensitive, and accurate assay for diazoxide in human plasma and urine samples was developed utilizing stable-isotope dilution-GC-mass fragmentography. 3-Trideuterodiazoxide (d 3-diazoxide) served as internal standard, and diazoxide was N-methylated with diazomethane prior to GC. Plasma elimination half-lives of diazoxide ranged within 20–53 hr in four severely hypertensive patients, which did not correlate with endogenous plasma creatinine levels. A rapid infusion over 10–15 sec of an antihypertensive dose presumably resulted in a very transient precipitation of diazoxide due to its limited solubility of approximately 380 Μg/ml plasma. Urinary excretion accounted for 4–6% of the dose within 24 hr after administration in the four patients studied and totalled 19% and 22% in two patients. Renal clearance of diazoxide was below 1 ml/min on the first day following administration and increased to 2–3 ml/min on consecutive days. It was concluded that renal excretion of diazoxide is self-limited by antihypertensive doses in severely hypertensive patients. The major route of elimination in these patients may be due to metabolism.
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  • 24
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 89-98 
    ISSN: 1573-8744
    Keywords: clindamycin ; clindamycin-2-palmitate ; clindamycin-2-hexadecylcarbonate ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To determine the bioavailability of clindamycin from the microbiologically inactive clindamycin-2-palmitate and clindamycin-2-hexadecylcarbonate in man, a three-way crossover study was conducted with oral administration of the two esters and clindamycin hydrochloride. In each case, serum clindamycin bioactivity concentrations were fitted to a one-compartment open model with an initial lag time. Analysis of variance of measured quantities (serum concentrations and urinary excretion) and of derived pharmacokinetic parameters showed that for every comparison except maximum serum concentrations clindamycin-2-palmitate was not significantly different (at p=0.05) from clindamycin hydrochloride. Clindamycin-2-hexadecylcarbonate gave significantly different values from those for the hydrochloride in all cases except the rate constant and half-life for elimination from the serum. The palmitate was the superior ester and was bioequivalent to the hydrochloride in man.
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