Pharmacokinetics, Bioequivalence, and Safety Evaluation of 2 Formulations of 10‐mg Rivaroxaban Tablets: A 4‐Period Crossover Trial

Abstract

AbstractThis study compared the safety, bioequivalence, and pharmacokinetic properties of 2 formulations of 10‐mg rivaroxaban tablets in healthy Chinese participants in fasting and fed arms. The trial was an open, randomized, 4‐period, replicated crossover scheme, and 36 volunteers were recruited separately for the fasting and fed arms. Volunteers were randomly administered a single dose of the test or reference formulation (10 mg) orally, followed by a 5‐day washout period. Rivaroxaban concentrations in the plasma were determined using liquid chromatography–tandem mass spectrometry, and pharmacokinetic parameters were obtained from the concentration‐time profiles. The mean values of the test and the reference product for the area under the plasma concentration–time curve from time 0 to the last measurable concentration, area under the plasma concentration–time curve from time 0 to infinity, and maximum plasma concentration were 996 and 1014 ng • h/mL, 1024 and 1055 ng • h/mL, and 150 and 152 ng/mL in the fasting arm, respectively; the values were 1155 and 1167 ng • h/mL, 1160 and 1172 ng • h/mL, and 202 and 193 ng/mL in the fed arm, respectively. All the parameters were within acceptable limits in terms of bioequivalence. No serious adverse events were observed. This study demonstrated that the 2 rivaroxaban tablets were bioequivalent in healthy Chinese participants under fasting and fed conditions.