A single and multiple postprandial dose study investigating the pharmacokinetics and pharmacodynamics of edoxaban in healthy Chinese volunteers

摘要

Aims: This study investigated the pharmacokinetics (PK) and pharmacodynamics (PD) of once-daily postprandial doses of edoxaban 60 mg in healthy Chinese subjects. Methods: 6 male and 6 female healthy Chinese volunteers, aged 18-45 years, were enrolled into this open-label, phase-I trial. Subjects received single oral doses of edoxaban 60 mg after a meal, followed by successive once-daily doses for 7 days. Serial blood samples were taken pre-and postdose to measure plasma concentrations of edoxaban and its major active metabolite D21-2393 as well as prothrombin time (PT) and activated partialprothrombin time (aPTT). Safety was assessed throughout the study. Results: Eoxaban was quickly absorbed after dosing. The resultant maximum and total exposure of edoxaban after single postprandial dose were similar to those after the same dose in fasting condition, but tmax was about half an hour longer. Meanwhile, the exposure of D21-2393 and the metabolite-over-parent ratio were both lower vs. the fasting condition, suggesting involvement of food on D21-2393 formation. Steady state was attained after two successive daily doses. The PK parameters of edoxaban with multiple postprandial doses were comparable to those observed in Caucasian and Japanese volunteers. Similarly, the PD profiles and the concentration-response relationship of edoxaban were not changed with repeated doses. Minor bleeding was the most commonly reported adverse event during the study. Conclusion: Once daily postprandial doses of edoxaban 60 mg was safe and well tolerated in healthy Chinese volunteers. The PK and PD characteristics of edoxaban were comparable among Chinese, Caucasian, and Japanese subjects.