Journal of Bioequivalence & Bioavailability

Abstract

Pharmacokinetic Equivalence Study of the Oral Direct Inhibitor of Factor Xa Anticoagulant, Rivaroxaban Film-Coated Tablets, in Healthy Subjects Under Fasting and Fed Conditions

Raymond R. Tjandrawinata*, Danang Agung Yunaidi, Yantirta Indra Kurniawan, Clarasintha Nindyatami, Ismail Dwi Saputro, Ima Aisyah Rahma, Vicky Achmad Ginanjar and Liana W. Susanto

Purpose: To evaluate the bioequivalence of two strengths of Rivaroxaban 10 mg and 20 mg film-coated tablets manufactured by PT Dexa Medica with the reference drug, Xarelto^® film-coated tablet, manufactured by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia.

Materials and Methods: Two studies were conducted separately under fasting condition for the 10 mg strength and fed condition for the 20 mg. The studies were open-label, randomized, single-dose, two-period, two-sequence, two-way crossover studies, which included 28 healthy adult male and female subjects in each study. The washout period was five days and 11 days for the 10 mg strength and 20 mg, respectively. The 10 mg study was completed by 28 subjects, whereas the 20 mg strength study was completed by 26 subjects. The plasma concentrations of Rivaroxaban were determined using validated Ultra-Performance Liquid Chromatography with Tandem Mass Spectrometry Detection (UPLC-MS/MS). The pharmacokinetic parameters assessed were Area Under the Curve (AUC_0–t), Area Under The Curve (AUC_0–∞), Maximum Concentration (C_max), Time-to-Maximum (T_max), and Half-life (t_½). Bioequivalence was established in the Test/Reference Geometric Means Ratio (GMR), and the 90% Confidence Interval (CI) of GMR was between 80.00 and 125.00% with 0.05 alpha for AUC_0-t and C_max.

Results: The GMR (90% CI) of the Test/Reference formulation of Rivaroxaban 10 mg was 91.51% (82.41%- 101.63%) for C_max and 98.32% (92.20%-104.83%) for AUC_0–t under fasting condition. The GMR (90% CI) of the Test/Reference formulation of Rivaroxaban 20 mg was 92.76% (87.60%-98.22%) for C_max and 94.35% (90.14%- 98.76%) for AUC_0–t under fed condition. The 90% CI of the test/reference drug from both strengths was within the bioequivalence acceptable range. Adverse events were reported in both studies, two in the 10 mg strength study and one in the 20 mg strength. All cases were mild, and no serious adverse events were reported.

Conclusion: The studies indicated that Rivaroxaban 10 mg and 20 film-coated tablets were bioequivalent with the reference drugs under fasting and fed conditions. The subjects well tolerated both formulations

Published Date: 2024-10-02; Received Date: 2024-09-02