Pharmacokinetic analysis of drug concentration data obtained during repetitive drug administration

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.