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

Abstract

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_max=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.

Keywords:

• Chinese
• edoxaban
• pharmacodynamics
• pharmacokinetics
• safety

Declaration of interest

The authors have no declarations of interest to report.