摘要
目的:研究盐酸司来吉兰片受试与参比制剂在中国健康受试者中空腹和餐后条件下的生物等效性.方法:共纳入84例健康受试者,空腹试验36例,餐后试验48例.空腹试验采用随机、开放、两序列、四周期、完全重复交叉设计,分为2组,每组18例;餐后试验采用随机、开放、三序列、三周期、部分重复交叉设计,分为3组,每组16例.每个周期分别单次口服盐酸司来吉兰片受试和参比制剂5 mg,清洗期均为14d.按计划的采血时间点采集静脉血,采用经验证的LC-MS/MS法测定血浆中司来吉兰、去甲基司来吉兰的药物浓度,用Phoenix WinNonlin 8.1软件计算药动学参数,评价两制剂的生物等效性.结果:空腹试验受试和参比制剂司来吉兰Cmax、AUC0-t、AUC0-∞分别为(2 265±1 849)和(2 810±2 658)pg·mL-1、(1 886±1831)和(1 996±2102)pg·mL-1·h、(1 938±1 860)和(2 051±2 133)pg·mL-1·h.餐后试验受试和参比制剂司来吉兰 Cmax、AUC0-t、AUC0-∞分别为(3 042±2 211)和(3 110±2 566)pg·mL-1、(4 081±3363)和(4 025±3 215)pg·mL-1·h、(4 175±3 448)和(4 129±3 307)pg·mL-1·h.空腹和餐后试验中受试和参比制剂主要药动学参数的几何均值比90％ CI均落在80.0％～125％.试验期共发生79例次(空腹28例次,餐后51例次)不良事件,未发生严重不良事件.结论:在空腹和餐后状态下,受试和参比制剂在健康受试者者中具有生物等效性,安全性良好.
Abstract
OBJECTIVE To study the bioequivalence of generic and original selegiline hydrochloride tablets in Chinese healthy subjects respectively under fasting and fed conditions.METHODS A total of 84 healthy subjects were enrolled in this study,including 36 cases of fasting administration and 48 cases of fed administration.The fasting administration trial was a ran-domized,open,two-sequence,four-cycle,completely repeated crossover design.The subjects were randomly divided into 2 groups,18 cases in each group.The fed administration trial was a randomized,open,three-sequence,three-cycle,partially repeated crossover design.The subjects were randomly divided into 3 groups,16 cases in each group.Single oral dose of 5 mg test and reference selegiline hydrochloride tablets was taken in each cycle,and the washout period was 14 days.The blood samples were obtained at the planned time points.Plasma concentrations of selegiline and desmethyl selegiline were determined by a validated LC-MS/MS method.Phoenix WinNonlin 8.1 software was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence of the two preparations.RESULTS The major pharmacokinetic parameters of the test and reference selegiline under fasting condition were as follows:Cmax(2 265±1 849)and(2 810±2 658)pg·mL-1,AUC0-t(1 886±1 831)and(1 996±2 102)pg·mL-1·h,AUC0-∞(1 938±1 860)and(2 051±2 133)pg·mL-1·h.The major pharmacokinetic parameters of the test and reference selegiline under fed condition were as follows:Cmax(3 042±2 211)and(3 110±2 566)pg·mL-1,AUC0-t(4 081±3 363)and(4 025±3 215)pg·mL-1·h,AUC0-∞(4 175±3 448)and(4 129±3 307)pg·mL-1·h.In the fasting and fed tests,the 90％CI of the geometric mean ratios of the main pharmacokinetic parameters between the test and reference prepara-tions were all within the range of 80％-125％,which met the criteria for bioequivalence evaluation.A total of 79 adverse events(28 under fasting condition and 51 under fed condition)occurred during the trial period,and no serious adverse event occurred.CONCLUSION In fasting and postprandial state,the test and reference preparations are bioequivalent and safe in healthy subjects..
NETL
NSTL
万方数据