Evaluation of Usefulness of Population Pharmacokinetic Analysis Considering Interindividual Variability of Bioavailability (3)

Abstract

We previously reported a positive correlation between the oral clearance (CL/F) and the apparent volume of distribution (V/F) of drugs with variable bioavailability (F). The aim of the present study using a computer simulation method was to further evaluate the usefulness of the population pharmacokinetic analysis model assuming the covariance of CL/F and V/F (ω_CL/F,V/F). We assumed variable bioavailability (F) not only in intestinal absorption, but also in hepatic first-pass extraction and transdermal absorption. The log likelihood difference (LLD) between the covariance and conventional (non-covariance) model analysis was very similar to the LLD between the true and conventional model analysis. The individual relative F (F_rel) values estimated with the covariance model analysis was also similar to the F_rel values estimated with the true model analysis. Therefore, we should use the covariance model and/or the true model positively for population pharmacokinetic analysis for drugs with variable F.