Renhua Zheng1, Dongwoo Kang2, Bo-Hyung Kim1
1Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine and Hospital, Seoul, Republic of Korea, 2Translational Medicine and Clinical Pharmacology, Daiichi Sankyo Pharma Development, Edison, NJ, USA
Objectives: The objective of this study is to evaluate the relative performance of population compartmental method vs NCA (non-compartmental analysis) approach in estimating the systemic exposures of drugs in BE (bioequivalence) studies.
Methods: Three BE study data were used for the comparison of population method vs NCA approach. The systemic exposures (Cmax, AUC) were calculated using the individual post hoc parameters of compartmental PK model from NONMEM®. The same systemic exposures were calculated using the NCA approach implemented in Phoenix® WinNonlin® 6.1. The results from the both methods were compared using geometric mean ratios of test/reference with 90% confidence intervals.
Results: The individual post hoc pharmacokinetic parameters along with the population parameters were estimated by NONMEM® using various sample sizes by resampling the data of the BE studies. The systemic exposures calculated from these pharmacokinetic parameters were similar between the test and reference formulations as based on the geometric mean ratios with 90% confidence intervals. Also, these exposures were comparable to those from non-compartmental methods.
Conclusions: These results indicate that the population modeling approach could be an alternative method for the bioequivalent assessment.
References:
[1] Pentikis HS, Henderson JD, Tran NL, Ludden TM. Bioequivalence: individual and population compartmental modeling compared to the noncompartmental approach. Pharm Res. 1996 Jul;13(7):1116-21.
Reference: PAGE 23 (2014) Abstr 3154 [www.page-meeting.org/?abstract=3154]
Poster: Methodology - Other topics