Pharmacokinetic analysis of drug concentration data obtained during repetitive drug administration. 1977

W A Colburn, and M Gibaldi

A digital computer curve-fitting method, designed to estimate pharmacokinetic model constants by utilizing all drug concentration-time data collected during repetitive dosing studies, was applied to data manifesting systematic dose-to-dose variability in one or another of the pharmacokinetic parameters. The method accurately determined dose-to-dose changes in absorption or elimination rate constants or in the apparent volume of distribution, and it would be useful for detecting phenomena such as self-induction and self-inhibition that may occur during multiple-dose administration. The method can also be used to analyze multiple-dose data of drugs exhibiting capacity-limited elimination and to obtain estimates of the Michaelis-Menten parameters.

UI MeSH Term Description Entries
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D003201 Computers Programmable electronic devices designed to accept data, perform prescribed mathematical and logical operations at high speed, and display the results of these operations. Calculators, Programmable,Computer Hardware,Computers, Digital,Hardware, Computer,Calculator, Programmable,Computer,Computer, Digital,Digital Computer,Digital Computers,Programmable Calculator,Programmable Calculators
D004364 Pharmaceutical Preparations Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013752 Tetracycline A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis. 4-Epitetracycline,Achromycin,Achromycin V,Hostacyclin,Sustamycin,Tetrabid,Tetracycline Hydrochloride,Tetracycline Monohydrochloride,Topicycline,4 Epitetracycline
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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