利伐沙班片在中国健康志愿者中的生物等效性研究  

Bioequivalence of rivaroxaban tablets in healthy Chinese subjects

作　　者：王华伟[1] 喻明[1] 李晓斌[1] 曹莹 隋鑫[1] 陈璐 窦晓燕 王诗婷 汪楠[1] 王文萍[1] WANG Hua-wei;YU Ming;LI Xiao-bin;CAO Ying;SUI Xin;CHEN Lu;DOU Xiao-yan;WANG Shi-ting;WANG Nan;WANG Wen-ping(PhaseⅠClinical Centre,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning Province,China)

机构地区：[1]辽宁中医药大学附属医院Ⅰ期临床试验病房,辽宁沈阳110032

出　　处：《中国临床药理学杂志》2020年第22期3590-3594,共5页The Chinese Journal of Clinical Pharmacology

基　　金：辽宁省“兴辽英才计划”基金资助项目(XLYC1802008);辽宁省自然科学基金资助项目(20180550690);辽宁省中药临床药物代谢动力学重点实验室基金资助项目(辽科发2005-16)。

摘　　要：目的研究利伐沙班片在中国健康人体内的生物等效性。方法空腹试验56例、餐后试验24例健康志愿者四周期、完全重复、自身交叉设计、单剂量口服利伐沙班片受试制剂或参比制剂10 mg,采用液相色谱-质谱法测定血浆中利伐沙班的血药浓度,应用WinNonlin 7.0软件计算药代动力学参数及相对生物利用度,判定两制剂是否等效。结果空腹试验受试制剂和参比制剂利伐沙班的主要药代动力学参数Cmax分别为(169.51±43.19)和(168.15±48.97)ng·mL^-1,AUC0-t分别为(1174.59±328.42)和(1141.41±291.05)h·ng·mL^-1,AUC0-∞分别为(1204.29±339.22)和(1165.03±294.94)ng·h·mL^-1。餐后试验受试制剂和参比制剂利伐沙班的主要药代动力学参数Cmax分别为(220.37±53.34)和(213.37±45.35)ng·mL^-1,AUC0-t分别为(1257.99±393.50)和(1256.73±327.40)ng·h·mL^-1,AUC0-∞分别为(1263.75±393.69)和(1262.67±327.44)ng·h·mL^-1。受试制剂与参比制剂Cmax、AUC0-t、AUC0-∞几何均值比的90%置信区间均完全落在80.00%~125.00%。结论 2种利伐沙班片在中国健康志愿者体内具有生物等效性。Objective To study the bioequivalence of rivaroxaban tablets in healthy Chinese subjects. Methods Fasting test in 56 subjects, postprandial test in 24 healthy subjects with four cycles, complete repetition, self-cross design, single dose oral rivaroxaban tablet test preparation or reference preparation 10 mg, the concentrations of rivaroxaban in plasma were determined by liquid chromatography-mass spectrometry. The main pharmacokinetic parameters and the relative bioavailability were calculated by WinNonlin 7.0 to determine whether the two preparations were equivalent. Results The pharmacokinetic parameters for test and reference preparations in fasting state were as follows: Cmax were(169.51±43.19) and(168.15±48.97)ng·mL^-1,AUC0-t were(1174.59±328.42)and(1141.41±291.05)ng·h·mL^-1,AUC0-∞ were(1204.29±339.22)and(1165.03±294.94)ng·h·mL^-1.The pharmacokinetic parameters for test and reference preparations in fed state were as follows: Cmax were(220.37±53.34)and(213.37±45.35)ng·mL^-1,AUC0-t were(1257.99±393.50)and(1256.73±327.40)ng·h·mL^-1,AUC0-∞ were(1263.75±393.69)and(1262.67±327.44)ng·h·mL^-1.The 90% confidence intervals of the geometric mean ratios of the test preparation and the reference preparation Cmax,AUC0-t,and AUC0-∞all fall completely within 80. 00%-125. 00%. Conclusion The test and reference preparations of rivaroxaban were bioequivalent in Chinese healthy subjects.

关 键 词：利伐沙班 生物等效性 液相 质谱 

分 类 号：R97[医药卫生—药品]