盐酸曲美他嗪片的生物等效性研究

Study of the Bioequivalence of Trimetazidine Hydrochloride Tablets in Chinese Healthy Volunteers

目的:研究盐酸曲美他嗪片的人体生物利用度和生物等效性。方法:22名男性健康受试者,随机双交叉口服剂量为20mg的受试制剂和参比制剂,采用LC-MS法测定血浆中盐酸曲美他嗪的浓度,使用DAS2.1.1软件对各药代动力学参数进行计算,同时对其生物等效性进行统计分析。结果:22名健康受试者服用20mg盐酸曲美他嗪片受试制剂和参比制剂的Cmax分别为(42.64±17.00)ng/ml和(41.32±19.66)ng/ml,Tmax分别为(2.2±1.5)h和(2.7±1.7)h,AUC0-t分别为(418.1±177.4)ng·h/ml和(397.8±147.1)ng·h/ml,AUC0-∞分别为(428.5±181.1)ng·h/ml和(407.9±150.5)ng·h/ml,t1/2分别为(5.9±1.6)h和(5.6±1.3)h。受试制剂中曲美他嗪Cmax的90%置信区间为参比制剂的100.1%～111.1%,AUC0-t的90%置信区间为参比制剂的97.0%～111.9%,AUC0-∞的90%置信区间为参比制剂的96.9%～111.9%。以AUC0-t计算,受试制剂中曲美他嗪的相对生物利用度为(105.9±18.6)%。结论:两制剂具有生物等效性。

Objective：To study the relative bioavailability and bioequivalence of domestic trimetazidine hydrochloride tablets in healthy subjects. Methods： In a randomized two-period reference and test crossover study, 22 healthy male volunteers were given a single oral dose of 20 mg trimetazidine hydrochloride. The concentration of trimetazidine hydrochloride in plasma were determined by LC-MS. The pharmacokinetic parameters were processed by DAS propram for statistic analysis.Results：The pharmacokinetic parameters of the test and reference tablets were as follows：Cmax were（42.64±17.00）ng/ml and （41.32±19.66）ng/ml;Tmax were（2.2±1.5）h and （2.7±1.7）h; AUC0-4 were（418.1±177.4）ng·h/ml and（397.8±147.1 ）ng·h/ml; AUC0-20 were （428.5±181.1）ng·h/ml and （407.9±150.5）ng·h/ml;t1/2 were （5.9±1.6）h and （5.6±1.3）h,respectively. The 90% confidential interval of Cmax,AUC0-4 and AUC0-∞ of tested formulation were 100.1%-111.1%, 97.0%- 111.9 % and 96.9%- 111.9%, respectively. The relative bioavailability of the test preparations was （ 105.9＋ 18.6）%.Conclusion： The domestic trimetazidine tablets are bioequivalent to the imported trimetazidine hydrochloride tablets.