Pharmacokinetics and Tolerability of Almorexant in Japanese and Caucasian Healthy Male Subjects

Background/Aims: The aim of this study was to compare the pharmacokinetics and tolerability of single doses of the dual orexin receptor antagonist almorexant in Japanese and Caucasian healthy male subjects (n = 10 in each group, body weight matched +/- 5%). Methods: Almorexant (200 mg) was administered in the morning in the fasted state. The pharmacokinetic parameters of almorexant were calculated by noncompartmental analysis from the plasma concentration data. Results: The pharmacokinetics of almorexant in Japanese and Caucasian subjects were similar. The plasma concentration-time profile of almorexant was characterized by a rapid absorption and disposition. Peak plasma concentrations (C(max)) were reached at approximately 1.0 h in both ethnic groups. C(max) was 13% lower (ratio of geometric means [90% CI]: 0.87 [0.53, 1.43]), and the total exposure (AUC(0-infinity)) was 15% lower (0.85 [0.54, 1.35]) in the Japanese subjects. There was no difference in the geometric mean ratio for t(1/2) between the two ethnic groups (1.03 [0.84, 1.25]). Almorexant was well tolerated in both ethnic groups. Conclusion: The pharmacokinetics and tolerability profiles of almorexant in Japanese and Caucasian healthy male subjects are similar. No dose adjustments for clinical studies with almorexant in Japanese subjects appear to be needed. Copyright (C) 2011 S. Karger AG, Basel