盐酸曲美他嗪缓释片在中国健康受试者中的生物等效性研究  

Bioequivalence of trimetazidine hydrochloride sustained release tablet in Chinese healthy subjects

作　　者：赵彩芸[1] 吕媛[1] 魏敏吉[1] 崔洪[1] 张朴[1] 夏亚红[1] 田继红[1] 裴莹子 产运霞 赵晓 马雁[1] 刘燕[1] 王茜 吴景 王雅泰 ZHAO Cai-yun;LÜYuan;WEI Min-ji;CUI Hong;ZHANG Pu;XIA Ya-hong;TIAN Ji-hong;PEI Ying-zi;CHAN Yun-xia;ZHAO Xiao;MA Yan;LIU Yan;WANG Xi;WU Jing;WANG Ya-tai(Institute of Clinical Pharmacology,Peking University First Hospital,Beijing 100034,China;Beijing Winsunny Pharmaceutical Co.Ltd.,Beijing 101113,China)

机构地区：[1]北京大学第一医院临床药理研究所,北京100034 [2]北京万生药业有限责任公司、北京福元药业股份有限公司,北京101113

出　　处：《中国临床药理学杂志》2021年第12期1483-1486,1490,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价盐酸曲美他嗪缓释片仿制药与原研药在中国健康受试者空腹和餐后条件下给药的生物等效性与安全性。方法按单中心、随机、开放、单剂量、两制剂、两序列、双周期、交叉研究设计,共纳入47例(空腹试验23例,餐后试验24例)成年男性和女性受试者随机交叉给药,分别单次口服受试制剂或参比制剂35 mg,用LC-MS/MS法测定血浆中曲美他嗪的浓度,用Win Nonlin 6.4软件按非房室模型计算药代动力学参数,并进行生物等效性评价。结果空腹组盐酸曲美他嗪缓释片受试制剂和参比制剂的主要药代动力学参数如下:C_(max)分别为(65.62±13.92)和(66.39±15.15)μg·L^(-1),t_(max)分别为(3.96±1.15)和(4.26±1.21)h,AUC_(0-t)分别为(909.43±219.81)和(920.65±230.09)μg·L^(-1)·h,AUC_(0-∞)分别为(921.57±226.17)和(933.35±236.56)μg·L^(-1)·h;餐后组盐酸曲美他嗪缓释片受试制剂和参比制剂的主要药代动力学参数如下:C_(max)分别为(69.78±14.65)和(65.99±13.73)μg·L^(-1),t_(max)分别为(4.83±0.82)和(4.71±1.00)h,AUC_(0-t)分别为(766.54±165.62)和(793.50±163.67)μg·L^(-1)·h,AUC_(0-∞)分别为(774.17±167.43)和(802.04±166.02)μg·L^(-1)·h。在空腹和餐后条件下,受试制剂和参比制剂主要药代动力学参数90%置信区间均在80.00%125.00%。结论空腹与餐后单次口服盐酸曲美他嗪缓释片仿制药与原研药在中国健康受试者体内均有生物等效性。Objective To compare the pharmacokinetic properties and bioequivalence of the domestic and imported trimetazidine hydrochloride sustained release tablets in Chinese healthy adults under fasting and fed conditions.Methods This was a single-center,randomized,open,label,single dose,two preparation,two period,crossover design.A total of 47 subjects(23 in fasting and 24 subjects in fed state)were given single oral dose 35 mg of test and reference trimetazidine hydrochloride sustained release tablets.The concentrations of trimetazidine in plasma were determined by LC-MS/MS method.The pharmacokinetic parameters were calculated and the bioequivalence was compared by non-compartment model of Win Nonlin 6.4 program.Results The main pharmacokinetics parameters of test and reference preparation of trimetazidine were as follows:in fasted state,C_(max)were(65.62±13.92)and(66.39±15.15)μg·L^(-1),t_(max)were(3.96±1.15)and(4.26±1.21)h,AUC_(0-t)were(909.43±219.81)and(920.65±230.09)μg·L^(-1)·h,AUC_(0-∞)were(921.57±226.17)and(933.35±236.56)μg·L^(-1)·h;in fed state,C_(max)were(69.78±14.65)and(65.99±13.73)μg·L^(-1),t_(max)were(4.83±0.82)and(4.71±1.00)h,AUC_(0-t)were(766.54±165.62)and(793.50±163.67)μg·L^(-1)·h,AUC_(0-∞)were(774.17±167.43)and(802.04±166.02)μg·L^(-1)·h.Under both conditions,the 90%confidence intervals of the main pharmacokinetic parameters of the test tablets and the reference tablets were between 80.00%and 125.00%,which met the criteria for bioequivalence evaluation.Conclusion Under both fasting and fed conditions,the domestic and imported trimetazidine hydrochloride sustained release tablets were bioequivalent in Chinese healthy adults.

关 键 词：盐酸曲美他嗪缓释片 中国健康受试者 生物等效性 

分 类 号：R97[医药卫生—药品]