Comparative pharmacokinetics of two formulations of 2.5-mg rivaroxaban in healthy Korean subjects.

Abstract

Objective: Rivaroxaban is a direct factor Xa inhibitor used for the prevention and treatment of thromboembolic disorders. The objective of this study was to compare the pharmacokinetic profiles of two rivaroxaban formulations after a single dose of rivaroxaban (2.5-mg tablet) in healthy Korean subjects.

Materials and methods: This study was a randomized, open-label, single-dose, two-period, crossover study that included 34 healthy adult subjects under fasting conditions. The test drug (Yuhan rivaroxaban tablet) or reference drug (Xarelto tablet) was administered in each period. Serial blood samples were collected up to 36 hours post-dose. Plasma concentrations were measured by LC-MS/MS. Pharmacokinetic parameters, including maximum plasma concentration (C_max) and area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC_t), were determined by non-compartmental analysis. The 90% confidence intervals (CIs) for the ratio of the geometric means of C_max and AUC_t for the test drug/reference drug were calculated to evaluate pharmacokinetic equivalence.

Results: A total of 28 subjects were included in the pharmacokinetic analysis. The geometric mean ratios (90% CI) of the test drug/reference drug for rivaroxaban were 1.0140 (0.9794 - 1.0499) for AUC_t and 0.9350 (0.8797 - 0.9939) for C_max. All adverse events (AEs) were mild, and there was no significant difference in the incidence of AEs between the formulations.

Conclusion: The pharmacokinetic parameters of rivaroxaban were compared between the test and reference drug, and both formulations were bioequivalent. The newly developed rivaroxaban tablet is safe and well tolerated as the reference drug (ClinicalTrials.gov identifiers: NCT05418803).