A single-dose study investigating the pharmacokinetics and pharmacodynamics of edoxaban at 30-90 mg in healthy Chinese volunteers.

1. This study investigated the pharmacokinetics and pharmacodynamics of single-dose edoxaban in healthy Chinese subjects. 2. This single-centre, open-label, 3-occasion, cross-over study enrolled six males and six females. Subjects received a single-oral-dose of edoxaban 30-90 mg in each study occasion under fasting condition. Serial blood samples were collected to measure the plasma concentrations of edoxaban and its major active metabolite D21-2393. Meanwhile, PT, INR, aPTT were measured pre- and post-dose. Safety was assessed. 3. After administration, edoxaban was rapidly absorbed (median T=1-2 h). With rapid transformation, peak concentration of D21-2393 was reached within 2-h post-dose. The elimination half-life of edoxaban was 5-20 h. The dose-exposure relationships were slightly lower-than-dose-proportional for both edoxaban and D21-2393. Although women had higher plasma exposure of edoxaban and D21-2393 than men, it was considered clinically insignificant. 4. The effects of edoxaban on all pharmacodynamic biomarkers were concentration-dependent and linearly-correlated to plasma level of the compound. Minor bleeding was the most commonly reported adverse events. 5. Single oral doses of edoxaban 30-90 mg were safe and well tolerated in healthy Chinese volunteers. 6. The pharmacokinetic and pharmacodynamic profiles of edoxaban in Chinese subjects were comparable to those observed in Caucasian and Japanese populations.