盐酸曲美他嗪片在中国健康志愿者中的生物等效性研究  

Bioequivalence of trimetazidine hydrochloride tablets in healthy Chinese volunteers

作　　者：朱珍真 郎丽巍 朱姗薇 王红艳[1] 宋占东 王丽珍 王敏 魏振满 ZHU Zhen-zhen;LANG Li-wei;ZHU Shan-wei;WANG Hong-yan;SONG Zhan-dong;WANG Li-zhen;WANG Min;WEI Zhen-man(Pharmacy Department,Medical Security Center Stationed in the 5th Medical Center Pharmacy Room,PLA General Hospital,Beijing 100039,China;Drug Trial Center,Chinese PLA Geneal Hospital,The 5th Medical Center,Beijing 100039,China)

机构地区：[1]解放军总医院医疗保障中心药剂科派驻第五医学中心药剂室,北京100039 [2]中国人民解放军总医院第五医学中心药物试验中心,北京100039

出　　处：《中国临床药理学杂志》2020年第16期2477-2481,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价2种盐酸曲美他嗪片在中国健康受试者的生物等效性及安全性。方法按单中心、开放、随机、单次给药、两制剂、两序列、两周期、交叉试验研究设计方法,空腹和餐后条件下分别入组健康受试者28例和24例,随机交叉单次口服受试制剂和参比制剂20 mg,用HPLC-MS/MS法测定血浆中曲美他嗪的浓度,用Phoenix WinNonlin(7.0版本)软件计算曲美他嗪的药动学参数,并进行生物等效性评价。结果受试者服用受试制剂和参比制剂后,空腹组血浆中曲美他嗪的主要药代动力学参数如下:Cmax分别为(59.31±13.89)和(56.63±10.36) ng·mL-1;AUC0-t分别为(528.16±142.91)和(534.64±142.04) ng·h·mL-1;AUC0-∞分别为(549.33±146.05)和(556.28±144.96) ng·h·mL-1。餐后组血浆中曲美他嗪的主要药代动力学参数如下:Cmax分别为(61.15±15.95)和(67.75±17.73) ng·mL-1;AUC0-t分别为(507.68±99.16)和(527.69±113.57) ng·h·mL-1;AUC0-∞分别为(527.05±99.66)和(546.25±114.92) ng·h·mL-1。2种制剂的Cmax、AUC0-t和AUC0-∞经对数转换后90%可信区间分别为空腹状态下97.94%~109.31%,94.45%~102.24%,94.58%~102.09%;餐后状态下82.69%~98.82%,93.86%~99.40%,94.31%~99.54%。结论 2种盐酸曲美他嗪片在中国健康受试者中具有生物等效性。Objective To evaluate the bioequivalence of two kinds of trimetazidine hydrochloride tablets in China healthy subjects. Methods This was a single-center, randomized, open-label, single-dose, two-period, cross-over pharmacokinetic study. A total of 28 subjects in fasting state and 24 subjects in fed state were given single oral dose of test and reference preparation of trimetazidine hydrochloride tablets(each 20 mg), respectively. The concentration of trimetazidine in human plasma was measured by HPLC-MS/MS. Main pharmacokinetic parameters were calculated by using Phoenix WinNonlin(V7.0) software. Results The main pharmacokinetic parameters of trimetazidine of the test and reference preparations were as follows: In fasting state, Cmax were(59.31±13.89),(56.63±10.36) ng·mL-1;AUC0-t were(528.16±142.91),(534.64±142.04) ng·h·mL-1;AUC0-∞ were(549.33±146.05),(556.28±144.96) ng·h·mL-1;In fed state, Cmax were(61.15±15.95),(67.75±17.73) ng·mL-1;AUC0-t were (507. 68 ± 99. 16),(527. 69 ± 113. 57) ng·h·mL-1;AUC0-∞ were(527. 05 ± 99. 66),(546. 25 ± 114. 92)ng·h·mL-1. The 90% confidential interval of Cmax,AUC0-t and AUC0-∞ of tested formulation in fasting state were 97. 94%-109. 31%, 94. 45%-102. 24%, 94. 58%-102. 09%;The above indexes in fed state were 82. 69%-98. 82%,93. 86%-99. 40%, 94. 31%-99. 54%. Conclusion Two kinds of trimetazidine hydrochloride tablets are determined to be bioequivalent.

关 键 词：曲美他嗪 药代动力学 血药浓度 生物等效性 

分 类 号：R97[医药卫生—药品]