Pharmacokinetics study and bioequivalence evaluation of Rivaroxaban Tablets in Chinese healthy subjects
Objective To study the pharmacokinetics of 2.5 mg Rivaroxaban Tablets in Chinese healthy subjects and evaluate the bioequivalence to the reference reagent.Methods 70 healthy subjects were administered oral 2.5 mg rivaroxaban test agent and reference reagent(Xarelto®).An open,single-dose,random,completely repeated and four-cycle crossover design was adopted.The subjects were divided into two groups,which are a single administration of the test(42 subjects)under fasting state and a single postprandial oral administration of the test(28 subjects).To calculate the main drug parameters,the LC-MS/MS was applied to determine the blood drug concentration at 18 different time points within 48 h after administration of the preparations.Bioequivalence was evaluated by using analysis of variance,two-sided one-sided t test,and 90％confidence interval analysis.Results After oral administration of test and reference preparation in fasting state,the main pharmacokinetic parameters Cmax,t1/2 and AUC0～t are(66.3±18.4)ng·mL-1,(4.76±1.73)h,(323.9±98.4)h·ng·mL-1 and(64.5±17.6)ng·mL-1,(4.45±1.47)h,(321.3± 104.5)h·ng·mL-1.The main pharmacokinetic parameters of Cmax,t1/2 and AUC0～t after oral administration of test and reference preparations after high-fat diet are(59.5±13.3)ng·mL-1,(5.14±1.24)h,(341.7±70.8)h·ng·mL-1 and(60.5±10.7)ng mL-1,(5.29±1.56)h,(348.8±77.6)h·ng·mL-1.The geometric mean ratio points of Cmax,AUC0～t and AUC0～∞ are between 80.00％to 125.00％,and the upper and lower limits of 90％confidence interval of variation rate within individuals were less than 2.5,the results indicated that the absorption degree,absorption rate and variation of rivaroxaban in test preparations were similar to reference preparations.Conclusion The LC-MS/MS method was used to determine the content of rivaroxaban in human plasma.The rivaroxaban(2.5 mg)test preparation and the reference preparation were bioequivalent when administered under fast state and after a high-fat diet.
NETL
NSTL
万方数据
维普
