Effect of food on the pharmacokinetics of darexaban, an oral direct factor Xa inhibitor, in healthy Japanese subjects.

BACKGROUND

Darexaban is a potent direct factor Xa (FXa) inhibitor developed for prophylaxis of venous and arterial thromboembolic disease. This drug is rapidly and extensively metabolized to darexaban glucuronide (YM-222714), which is a pharmacologically active metabolite. The potential effects of food on the harmacokinetics of darexaban glucuronide after darexaban administration were assessed in two studies.

METHODS

Both studies were conducted as open-label, two-way crossover studies. Healthy non-elderly Japanese male subjects received darexaban as a single 15 mg tablet (Study 1, n = 24) or a single 30 mg tablet (Study 2, n = 24). The geometric mean ratio (GMR) (fed/fasted) for AUClast and Cmax were evaluated as primary parameters.

RESULTS

GMR(fed/fasted) for AUClast emonstrated slight decreases as 0.797 (90% CI: 0.758 - 0.838) in Study 1 and 0.821 (90% CI: 0.752 - 0.896) in Study 2. For Cmax, the GMR was 0.908 (90%CI: 0.835 - 0.988) in Study 1 and 1.039 (90% CI: 0.953 - 1.131) in Study 2. There were no serious adverse events during the two studies. None was considered to be drug-related.

CONCLUSION

These studies demonstrated that there was no clinically significant effect of food on the pharmacokinetics after administration of darexaban. We therefore conclude that darexaban can be administered without regard to food intake.