Bioequivalence: individual and population compartmental modeling compared to the noncompartmental approach.
OBJECTIVE
The purpose of this study were to evaluate the use of individual compartmental and population compartmental methods for bioequivalence 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 PCNONLIN using individual compartmental modeling and NONMEM for population analyses. These results were compared with results obtained from the traditional noncompartmental or SHAM (slopes, heights, areas, and moments) approach for bioequivalence assessment and the 90% confidence interval procedure.


RESULTS
Individual compartmental modeling and population compartmental modeling techniques performed well on this routine set of bioequivalence data which displayed simple pharmacokinetic properties. A direct assessment of the analysis methods was made by comparing the final estimates and 90% confidence intervals for the test to reference ratios (T/R) of AUC and CMAX. The final estimates and 90% confidence intervals for AUC T/R and CMAX T/R were similar and suggest consistency of results, independent of the method used.


CONCLUSIONS
These results demonstrate the utility of modeling techniques as adjuncts to the traditional noncompartmental approach for bioequivalence determination.
Pentikis
H S
HS
Division of Biopharmaceutics, Food and Drug Administration, Rockville, Maryland 20857, USA.
Henderson
J D
JD
Tran
N L
NL
Ludden
T M
TM
D002752:Chlorthalidone / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D006801:Humans; D015233:Models, Statistical; D013810:Therapeutic Equivalency
D002752:Chlorthalidone