AIM: Study on the bioequivalence of rivaroxaban tablets from two different manufacturers in healthy subjects under fasting and postprandial conditions. METHODS: Adopting a single center, randomized, open, fasting and postprandial, four cycle, fully repeated crossover trial design. 28 healthy male and female subjects were given oral administration of either the test or reference formulation (10 mg) on an empty stomach or in a postprandial state, with a cleaning period of 7 days between cycles. The concentration of rivaroxaban in the plasma (heparin sodium) of the subjects was measured using liquid chromatography tandem mass spectrometry (LC-MS/MS), and pharmacokinetic (PK) parameters were calculated using Phoenix WinNonlin 7.0 software to evaluate the bioequivalence of the test and reference formulations. RESULTS: Fasting group: After oral administration of the investigational drug, the Cmax of the test formulation and reference formulation were (200.96±68.99) ng/mL and (196.96±50.97) ng/mL, respectively, and the AUC0-t were (1 439.93±493.94) h·ng·mL-1 and (1 395.90±411.49) h·ng·mL-1, respectively, the AUC0-∞ were (1 506.56±511.47) h·ng·mL-1 and (1 451.94±417.89) h·ng·mL-1, respectively, the 90% confidence intervals for the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ were 91.87%-103.37%,95.00%-105.07%,95.33%- 105.57%, respectively, the 90% CI of the intra-individual standard deviation ratio (SWT/SWR) for Cmax, AUC0-t, AUC0-∞ were 0.88-1.73, 0.74-1.45 and 0.72-1.41, respectively. Postprandial group: After oral administration of the experimental drug, the Cmax of the test and reference formulations were (241.23±54.44) ng/mL and (226.54±48.04) ng/mL, respectively, and the AUC0-t were (1 383.26±437.05) h·ng·mL-1 and (1 333.54±372.53) h·ng·mL-1, respectively, the AUC0-∞ were
(1 404.01±439.89) h·ng·mL-1 and (1 352.31±374.45) h·ng·mL-1, respectively, the 90% confidence intervals for the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ were 100.92%-110.50%, 98.30%-108.31%, and 98.46%-108.39%, respectively, the 90%CI of the intra-individual standard deviation ratio (SWT/SWR) for Cmax, AUC0-t and AUC0-∞ were 0.63-1.29, 0.78-1.61 and 0.79-1.61, respectively. CONCLUSION: Bioequivalence of the two preparations in fasting and postprandial state in healthy subjects.
