PHARMACOKINETIC ANALYSIS OF DRUG CONCENTRATION DATA OBTAINED DURING REPETITIVE DRUG ADMINISTRATION

A digital computer method that uses all drug concentration-time data collected during repetitive dosing studies was developed to simultaneously estimate pharmacokinetic parameters and fit the data. The method utilizes the nonlinear least-squares regression program NONLIN. It can accommodate changes in dose and dosing interval during the regimen and it permits curve fitting on the basis of one of a number of linear pharmacokinetic models. Theoretical data containing 10% uniformly distributed pseudorandom error and experimental data from 3 clinical studies were used to validate the method. Reasonably precise and accurate parameter estimates and good curve fits were obtained.