Comparison of MK-0767 pharmacokinetics in Japanese and non-Japanese subjects

Abstract

An analysis was performed to compare preliminary pharmacokinetics (PK) of MK-0767, a dual PPARα/γ agonist, between Japanese and non-Japanese populations after single and multiple oral doses of MK-0767. The PK data from available MK-0767 Phase I studies in a non-Japanese population (5 studies) were pooled (single dose and multiple dose studies separately) and compared to that from Phase I studies in a Japanese population (2 studies). The analysis included single doses from 1- to 10-mg and multiple doses from 0.3- to 25–mg at steady state; all subjects included in this analysis were young healthy male volunteers. An analysis of covariance (ANCOVA) model was used with a factor for population and covariates age, weight, height, and log transformed dose level. To assess the magnitude of the difference between the two populations with respect to AUC and Cmax, the geometric mean ratio (GMR) (Japanese/non-Japanese) with 90% confidence intervals (CIs) were provided based on the above ANCOVA model. Following single doses, the dose-adjusted AUC(0-∞) GMR was 0.89 with a 90% CI of (0.78, 1.02) and the dose-adjusted Cmax GMR was 1.00 with a 90% CI of (0.89, 1.12). Following multiple doses at steady state, the dose-adjusted AUC(0-24hr) GMR was 1.18 with a 90% CI of (0.99, 1.40) and the dose-adjusted Cmax GMR was 1.13 with a 90% CI of (0.95, 1.33). Based on this analysis, pharmacokinetics of MK-0767 are similar in Japanese and non-Japanese subjects. Clinical Pharmacology & Therapeutics (2004) 75, P11–P11; doi: 10.1016/j.clpt.2003.11.040