摘要
目的:评价盐酸曲美他嗪缓释片在中国健康受试者空腹和餐后条件下单剂量给药时的人体生物等效性。方法:采用随机、开放、单剂量、两序列、两周期交叉的试验设计。空腹组和餐后组分别纳入24例健康受试者,并随机分为两组,每组12例,口服盐酸曲美他嗪缓释片受试制剂(T)或参比制剂(R)35 mg,第一组按照TR的给药序列,第二组按照RT的给药序列给药。采用高效液相色谱-串联质谱对血浆中曲美他嗪浓度进行测定。利用Win Nonlin 6.4及以上版本和SAS 9.3版本软件进行药代动力学参数的计算和统计分析,并进行生物等效性评价。结果:空腹口服参比制剂和受试制剂后的主要药代动力学参数如下:C_(max)分别为(69.73±12.86)和(74.43±13.45)ng·m L^(-1);T_(max)均为4.5 h;t_(1/2)分别为(6.47±0.51)和(6.38±0.42)h;AUC_(0-t)分别为(825.74±140.29)和(867.88±126.28)ng·mL^(-1)·h;AUC_(0-∞)分别为(832.57±142.73)和(874.50±127.86)ng·mL^(-1)·h。餐后口服参比制剂和受试制剂后的主要药代动力学参数如下:C_(max)分别为(80.05±16.67)和(90.40±17.95)ng·mL^(-1);T_(max)均为4.5 h;t_(1/2)分别为(6.32±1.02)和(6.17±1.00)h;AUC_(0-t)分别为(824.61±147.04)和(825.27±154.35)ng·m L^(-1)·h;AUC_(0-∞)分别为(831.34±149.00)和(831.43±156.99)ng·m L^(-1)·h。在空腹和餐后状态下,受试制剂和参比制剂主要药代动力学参数几何均值对应的90%置信区间符合等效范围要求(80.00%~125.00%)。结论:受试制剂和参比制剂在空腹和餐后组口服时均具有生物等效性。
Objective:To evaluate the human bioequivalence of trimetazidine hydrochloride sustained release tablets in Chinese healthy subjects with single dose in fasting and postprandial conditions.Methods:A randomized,open,single-dose,two-sequence,two-cycle crossover trial design was used.Twenty-four healthy subjects were included in the fasting and postprandial groups,respectively,and randomly divided into two groups with 12 subjects in each group.Trimetazidine hydrochloride sustained release tablet test preparation(T) or reference preparation(R) 35 mg was administered orally according to TR sequence in the first group and RT sequence in the second group.The concentration of trimetazidine in plasma was determined by high performance liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated and statistically analyzed by Win Nonlin 6.4 and above and SAS 9.3,and the bioequivalence was evaluated.Results:The main pharmacokinetic parameters of reference preparation and test preparation after fasting were as follows:C_(max) were(69.73±12.86) and(74.43±13.45) ng·mL~(-1),respectively.T_(max) were all 4.5 h.t_(1/2) were(6.47±0.51) and(6.38±0.42) h,respectively.AUC_(0-t) were(825.74±140.29) and(867.88±126.28) ng·mL~(-1)·h,respectively.AUC_(0-∞) were(832.57±142.73) and(874.50±127.86) ng·mL~(-1)·h,respectively.The main pharmacokinetic parameters of reference preparation and test preparation after oral administration after meals were as follows:C_(max) were(80.05±16.67)and(90.40±17.95) ng·mL~(-1),respectively.T_(max) were all 4.5 h.t_(1/2) were(6.32±1.02) and(6.17±1.00) h,respectively.AUC_(0-t) were(824.61±147.04) and(825.27±154.35) ng·mL~(-1)·h,respectively.AUC_(0-∞) were(831.34±149.00) and(831.43±156.99) ng·mL~(-1)·h,respectively.90% confidence intervals corresponding to geometric means value of main pharmacokinetic parameters of test preparation and reference preparation met the requirements of equivalent range(80.00%~125.00%) in fasting and postprandial states.Conclusion:The test preparation and reference preparation are bioequivalent when taken orally in fasting and postprandial groups.
作者
冯巧巧
纪红英
梁蕊
樊红延
温清
Feng Qiaoqiao;Ji Hongying;Liang Rui;Fan Hongyan;Wen Qing(Shandong Center for Food and Drug Evaluation&Inspection,Jinan 250014,China;Shandong First Medical University,Jinan 250062,China;Central Hospital Affi liated to Shandong First Medical University,Jinan 250013,China)
出处
《中国药事》
CAS
2023年第8期954-960,共7页
Chinese Pharmaceutical Affairs
