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Pharmacokinetic Analysis of Drug Concentration Data Obtained during Repetitive Drug Administration

1977; Elsevier BV; Volume: 66; Issue: 4 Linguagem: Inglês

10.1002/jps.2600660417

1520-6017

Colburn Wayne A, Milo Gibaldi,

Innovative Microfluidic and Catalytic Techniques Innovation

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.