卡托普利片在中国健康受试者的生物等效性研究

Bioequivalence study of captopril tablets in Chinese healthy subjects

目的 评价空腹状态下单剂量口服卡托普利片受试制剂与参比制剂的生物等效性及安全性。方法 采用单中心、单剂量、开放、随机、2周期、双序列、自身交叉试验设计。24例健康受试者被随机分为TR组和RT组,每组12例。每周期单次空腹口服卡托普利片受试制剂或参比制剂25 mg。用经方法学验证的LC-MS/MS法测定血浆中卡托普利的浓度,用Phoenix WinNonlin软件(Pharsight Company,V7.0)计算其主要药代动力学参数,评价2种制剂的生物等效性。结果 受试者空腹口服受试制剂和参比制剂后,血浆中卡托普利的主要药代动力学参数如下:C_(max)分别为(883.79±147.60)和(838.50±164.20)ng·mL^(-1);AUC_(0-t)分别为(3 455.06±613.75)和(3 408.14±445.72)h·ng·mL^(-1);AUC_(0-∞)分别为(3 694.68±648.63)和(3 664.34±461.39)h·ng·mL^(-1);T_(max)分别为0.75(0.5,1.5)和0.75(0.5,1.25)h;t_(1/2)分别为(7.58±0.66)和(7.80±0.83)h。受试制剂与参比制剂C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比值的90%置信区间分别为98.62%~113.21%,95.84%~105.21%和95.23%~104.71%,均落在80.00%~125.00%范围内。结论 空腹状态下卡托普利片受试制剂和参比制剂具有生物等效性。

Objective To evaluate the bioequivalence and safety of single-dose oral captopril tablets in fasted state between test preparation and reference preparation.Methods A single-center,single-dose,open-label,randomized,two-cycle,two-sequence,self-crossover trial design was used in this study.Twenty-four healthy subjects were randomized into TR and RT groups,12 in each group.A single fasted oral dose of 25 mg of the test or reference formulation of captopril tablets was administered per cycle.The concentration of captopril in plasma was determined by LC-MS/MS method verified by methodology,and its main pharmacokinetic parameters were calculated by Phoenix Win Nonlin software (Pharsight Company,V7.0) to evaluate the bioequivalence of the two preparations.Results The main pharmacokinetic parameters of captopril in plasma after fasting po of test and reference preparations were as follows:C_(max)were (883.79±147.60) and (838.50±164.20)ng·mL^(-1);AUC_(0-t)were (3 455.06±613.75) and (3 408.14±445.72)h·ng·mL^(-1);AUC_(0-∞)were (3 694.68±648.63) and(3 664.34±461.39) h·ng·mL^(-1);T_(max)were 0.75 (0.5,1.5) and0.75 (0.5,1.25) h;t_(1/2)were (7.58±0.66) and (7.80±0.83) h.The 90%confidence intervals for the geometric mean ratios of C_(max),AUC_(0-t)and AUC_(0-∞)of the tested formulations to the reference formulation were98.62%-113.21%,95.84%-105.21%and 95.23%-104.71%,all falling within the range of 80.00%-125.00%.Conclusion The test and reference formulations of captopril tablets were bioequivalent under fasting conditions.