摘要
目的研究多剂量口服马来酸曲美布汀缓释片在中国健康人体内的药动学特征和生物等效性。方法 26名健康男性志愿者随机交叉多剂量早晚口服马来酸曲美布汀缓释片受试制剂或参比制剂300 mg,每日2次,连续6 d。采用HPLC-MS/MS测定血浆中曲美布汀和N-去甲基曲美布汀浓度,用DAS2.1药动学程序计算药动学参数,并进行生物等效性评价。结果多剂量口服马来酸曲美布汀受试和参比制剂后,血浆曲美布汀Cmax分别为(35.668?22.196),(33.022?16.077)ng·m L?1,tmax分别为(3.154?1.875),(0.365?9.946)h,t1/2分别为(20.793?13.305),(16.989?4.707)h,AUCss分别为(252.075?150.358),(224.106?95.405)ng·h·m L?1;血浆N-去甲基曲美布汀Cmax分别为(1 571.809?823.169),(1 623.535?536.813)ng·m L?1,tmax分别为(?0.250?11.259),(2.481?1.237)h,t1/2分别为(9.796?2.450),(9.220?2.009)h,AUCss分别为(11 254.863?5 746.620),(10 911.059?4 111.751)ng·h·m L?1。受试制剂和参比制剂主要药动学参数均无显著性差异。结论马来酸曲美布汀受试制剂与参比制剂具有生物等效性。
OBJECTIVE To explore the pharmacokinetics and bioequivalence of trimebutine maleate sustained-release tablets with multiple dose administration in healthy Chinese volunteers. METHODS A multiple oral dose（300 mg of test or reference preparation twice a day for 6 days） were given to 26 male healthy volunteers in a randomized crossover study. The concentration of trimebutine and N-demethyl trimebutine in plasma were determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated and the bioequivalence of 2 formulations were evaluated by DAS program. RESULTS After multiple dose, the pharmacokinetic parameters of the test and reference trimebutine were as follows： Cmax were（35.668±22.196）,（33.022±16.077）ng·m L^-1, tmax were（3.154±1.875）,（0.365±9.946）h, t1/2 were（20.793±13.305）h and（16.989±4.707）h, AUCss were（252.075±150.358）,（224.106±95.405）ng·h·m L^-1, respectively. Meanwhile, the pharmacokinetic parameters of N-demethyl trimebutine were as follows： Cmax were（1 571.809±823.169）,（1 623.535±536.813）ng·m L^-1, tmax were（±0.250±11.259）,（2.481±1.237）h, t1/2 were（9.796±2.450）,（9.220±2.009）h, AUCss were（11 254.863±5 746.620）,（10 911.059±4 111.751）ng·h·m L^-1, respectively. CONCLUSION The test and reference preparation of trimebutine are bioequivalent.
出处
《中国现代应用药学》
CAS
CSCD
2016年第4期461-466,共6页
Chinese Journal of Modern Applied Pharmacy
基金
科技部重大专项项目(2012ZX09303018001)
同济医院新技术新业务项目(2201300388)
