PHARMACOKINETICS AND BIOEQUIVALENCE ASSESSMENT OF ORAL RIVAROXABAN TABLET IN IRANIAN HEALTHY VOLUNTEERSAbstract
Rivaroxaban is utilized as a direct factor Xa inhibitor for the prevention and remedy of thromboembolic disorders. This study aimed to evaluate a generic version of rivaroxaban 10 mg tablet. Considering previous reports of safety and tolerability of a single dose (1.25-80 mg) of rivaroxaban, this study used a randomized, single-dose two-way crossover of rivaroxaban in 28 healthy volunteers, with a washout period of seven days. Analyses of blood samples were performed by a validated ultra-high performance liquid chromatography coupled with tandem mass spectrometry. An YMC-Pack ODS-AQ reversed-phase column with the mobile phase of acetonitrile and 10 mM ammonium acetate pH = 3 (70:30, v/v) at a flow rate of 0.3 mL.min-1 under isocratic elution was selected for the analysis. A range of 2.5-600 ng.mL-1 was obtained for the calibration curve. Pharmacokinetic parameters were calculated for the bioequivalence assessment. The results showed that two formulations have similar pharmacokinetics. The 90% confidence interval of the mean ratios of the test versus reference formulation of Ln transformed AUC0-30 (82.0-98.0), AUC0-inf (81.3-105.2), and Cmax (82.4-104.4) were within the acceptable range of 80-125%.
M. Dibaei, A. Haghighi, A. A. Golabchifar, K. Sadeghi, N. Pourghasem, A. Tavassoli and M. R. Rouini *
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
20 November 2018
07 March 2019
29 March 2019
01 October 2019