Bioequivalence and Pharmacokinetic Study of 2 Edoxaban Tablets in Healthy Chinese Subjects

Abstract The aim was to investigate the bioequivalence of 2 orally administered edoxaban 60‐mg tablets and the food effects on the pharmacokinetics of edoxaban. Sixty‐four healthy Chinese subjects participated in this open‐label, randomized, 2‐sequence, 4‐period, crossover study. All subjects randomly received 60‐mg generic (test) or branded (reference) edoxaban tablet in each period. Plasma edoxaban concentrations were determined using liquid chromatography–tandem mass spectrometry. The pharmacokinetic parameters maximum concentration (C max ) and area under the concentration‐time curve (AUC) were compared to assess bioequivalence. The geometric least‐squares mean ratios for C max , AUC from time 0 to the last measurable time point (AUC 0‐t ), and AUC from time 0 extrapolated to infinity (AUC 0‐∞ ) were 97.0%, 95.4%, and 96.1%, respectively, in the fasting test, and 98.6%, 100.0%, and 99.8%, respectively, in the fed test. Food increased exposure and prolonged the time to maximum concentration of edoxaban. Both formulations displayed comparable safety profiles, with no serious adverse events reported. The 2 products of edoxaban tablets are bioequivalent and safe in healthy Chinese volunteers. Food may have a modest effect on the pharmacokinetic properties of edoxaban.