Bioequivalence and Food Effect Assessment Between 2 Oral Tablet Formulations of Rivaroxaban 20 mg in Healthy Chinese Subjects.

Abstract

To evaluate the bioequivalence and safety of oral rivaroxaban tablets between a test formulation and a reference formulation in healthy Chinese subjects, a randomized, open, 2-formulation, 4-cycle, complete repeat crossover study was conducted under both fasting and fed states. Thirty-six healthy participants were enrolled separately for the fasting and fed groups, and each subject received a single oral dose of 20 mg of the test or reference formulation of rivaroxaban tablets per cycle. Blood samples were collected at specified intervals, and rivaroxaban was analyzed using liquid chromatography-tandem mass spectrometry. Under fasting and fed conditions, the 90% confidence intervals (CIs) for the geometric mean ratios of the maximum concentration (C_max), the area under the plasma concentration-time curve from time 0 to the last measurable time point (AUC_0-t), and the area under the curve extrapolated to infinity from time 0 (AUC_0-∞) all fell within the 80%-125% CI, and the upper limit of the 90% CIs for the test-to-reference ratio of the within-subject variability was <2.5. This indicated that the test formulation of rivaroxaban is bioequivalent to the reference formulation. Compared to the fasted state, the C_max, AUC_0-t, and AUC_0-∞ of rivaroxaban increased significantly by factors of 2, 1.6, and 1.5, respectively, following oral administration of 20 mg of rivaroxaban in the fed state. This suggests that a high-fat diet significantly enhances the exposure to rivaroxaban. No serious adverse events were reported under fasting or fed conditions.