BIOEQUIVALENCE - INDIVIDUAL AND POPULATION COMPARTMENTAL MODELING COMPARED TO THE NONCOMPARTMENTAL APPROACH

Purpose. The purposes of this study were to evaluate the use of indivi dual compartmental and population compartmental methods for bioequival ence determination, and to determine their utility as adjuncts to the current methods used for bioequivalence assessment. Methods. Data from three bioequivalence studies of chlorthalidone were analyzed with PCN ONLIN using individual compartmental modeling and NONMEM for populatio n analyses. These results were compared with results obtained from the traditional noncompartmental or SHAM (slopes, heights, areas, and mom ents) approach for bioequivalence assessment and the 90% confidence in terval procedure. Results. Individual compartmental modeling and popul ation compartmental modeling techniques performed well on this routine set of bioequivalence data which displayed simple pharmacokinetic pro perties. A direct assessment of the analysis methods was made by compa ring the final estimates and 90% confidence intervals for the test to reference ratios (T/R) of AUC and CMAX. The final estimates and 90% co nfidence intervals for AUC T/R and CMAX T/R were similar and suggest c onsistency of results, independent of the method used. Conclusions. Th ese results demonstrate the utility of modeling techniques as adjuncts to the traditional noncompartmental approach for bioequivalence deter mination.