This study aimed to evaluate the bioequivalence (BE) of 2 formulations of the 10-mg rivaroxaban tablet. The study was a randomized, open-label, 4-period, crossover study that included 28 healthy subjects in fasting or fed conditions. The pharmacokinetic parameters were determined based on the concentrations of rivaroxaban using high-performance liquid chromatography with a tandem mass spectrometer detector. In each of the 4 study periods with fasting or fed conditions, a single dose of test or reference product was administered. Rivaroxaban concentrations in plasma were determined using a validated liquid chromatography with a tandem mass spectrometer detector method. The pharmacokinetic parameters assessed were the area under the plasma concentration-time curve (AUC0-t , AUC0-∞ ), the peak plasma concentration of the drug (Cmax ), time to achieve Cmax , elimination half-life, within-subject variability of test drug, and within-subject variability of reference drug. The geometric mean ratio (90%CI) of the test drug/reference drug for rivaroxaban was 90.38% to 103.60% for AUC0-t in fasting conditions and 90.13% to 100.42% in fed conditions. The AUC0-∞ s were 89.94% to 102.50% and 90.14% to 100.45% under fasting and fed conditions, respectively. The Cmax values were 90.58% to 105.01% and 96.36% to 108.07% in these 2 conditions, respectively. All 90%CIs for test drug/reference drug geometric mean ratio were ≤2.5. The 90%CIs for test/reference AUC ratio and Cmax ratio were within the acceptable range for BE. There were no adverse events encountered during this BE study. The study's results indicated that the 2 formulations of the rivaroxaban tablet were bioequivalent.
Keywords: bioequivalence; narrow-therapeutic-index drug; pharmacokinetic; rivaroxaban.
© 2019, The American College of Clinical Pharmacology.