盐酸特拉唑嗪片在中国健康受试者中的生物等效性研究

Bioequivalence of hydrochloride terazosin tablets in Chinese healthy subjects

目的研究盐酸特拉唑嗪片仿制药与原研药在中国健康受试者中单剂量空腹条件下给药的生物等效性。方法用单中心、随机、开放、单次给药、两制剂、两周期、双交叉试验设计,共纳入24例成年男性和女性受试者随机交叉给药。分别单次口服盐酸特拉唑嗪片受试制剂和参比制剂2 mg,用液相色谱串联质谱法测定血浆中特拉唑嗪的浓度。用Phoenix WinNonlin 8.0软件计算主要药代动力学(PK)参数。结果空腹组的盐酸特拉唑嗪片受试制剂和参比制剂主要PK参数:Cmax分别为(53.79±9.77)和(57.62±14.18)ng·mL^(-1),AUC0-t分别为(519.90±179.49)和(551.99±143.15)ng·mL^(-1)·h,AUC0-∞分别为(565.59±161.15)和(576.91±149.43)ng·mL^(-1)·h,tmax分别为1.00(0.28,2.02)和0.75(0.50,1.67)h,t1/2分别为(10.35±1.71)和(10.30±1.61)h。在空腹条件下,受试制剂与参比制剂主要PK参数的90%置信区间均在80.00%~125.00%。结论在空腹条件下,中国健康成年受试者单次口服盐酸特拉唑嗪片仿制药与原研药具有生物等效性。

Objective To study the bioequivalence of generic and original hydrochloride terazosin tablets in Chinese healthy subjects after single dose under fasting conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 24 healthy adult male and female subjects were included in the random crossover administration.Single oral dose 2 mg of test and reference were taken,respectively.Plasma concentration of terazosin was determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.O software.Results The main pharmacokinetic parameters of the test and reference preparations of hydrochloride terazosin tablets in the fasting group were as follows:C,max were(53.79±9.77)and(57.62±14.18)ng·mL^(-1),AUCo-t were(519.90±179.49)and(551.99±143.15)ng·mL^(-1).h,AUCo-αwere(565.59±161.15)and(576.91±149.43)ng·mL^(-1).h,tmx were 1.00(0.28,2.02)and 0.75(0.50,1.67))h,ti/2were(10.35±1.71)and(10.30±1.61)h.Under fasting conditions,the 90%confidence intervals of the main pharmacokinetic parameters of the test and reference preparations were in the range of 80.00%-125.00%.Conclusion Under fasting conditions,a single oral dose of generic and original hydrochloride terazosin tablets in Chinese healthy adult volunteers showed bioequivalence.