国产与进口来曲唑的人体生物等效性研究

目的:研究国产来曲唑胶囊在人体的相对生物利用度,并与进口片比较,评价两者生物等效性.方法:20名健康男性志愿者随机交叉单剂量口服国产来曲唑胶囊(受试制剂)或进口来曲唑片(参比制剂)2.5 mg后,采用液相色谱串联质谱法测定血药浓度,用DAS2.0软件计算药动学参数,并评价其生物等效性.结果:单次口服来曲唑受试制剂或参比制剂2.5 mg后,药动学参数分别为:Cmax(28.83± 6.74)和(29.44±7.13)ng·ml-1;Tmax(1.1±0.4)和(0.9±0.3)h;t1/2(58.6±13.2)和(57.9±13.5)h;AUC 0-216(1590±412)和(1546±389)ng·h·ml-1;AUC0-∞(1 733±472)和(1 683±440)ng·h·ml-1.受试制剂的相对生物利用度为(103.7±18.3)%;受试制剂中来曲唑的Cmax、AUC0-216、AUC0-∞的90%置信区间分别为91.8%～105.2%、97.8%～107.5%、96.5%～108.8%.结论:国产来曲唑胶囊与进口来曲唑片在人体内生物等效.

Study on the Bioequivalence of Domestic and Imported Letrozole in Healthy Volunteers

Objective: To study the relative bioavailability of domestic letrozole oral preparation in healthy volunteers and evaluate the bioequivalence of domestic and imported letrozole preparation.Method: A randomized crossover design was performed in 20 healthy male volunteers.A single oral dose of 2.5 mg domestic capsules(test preparation) or imported tablets(reference preparation) was administrated.Plasma concentrations of letrozole were measured by LC-MS/MS.The pharmacokinetic parameters were calculated by DAS 2.0 software and the bioequivalence was evaluated.Result: After a single oral dose of 2.5 mg letrozole test or reference preparation,the main pharmacokinetic parameters were as follows: Cmax of(28.83±6.74) and(29.44±7.13)ng·ml-1;Tmax of(1.1±0.4)and(0.9±0.3)h,t1/2 of(58.6±13.2) and(57.9±13.5)h,AUC0-216 of(1 590±412)and(1 546±389)ng·h·ml-1,AUC0-∞ of(1 733±472)and(1 683±440)ng·h·ml-1.The relative bioavailability was(103.7±18.3)%.The 90% confidence interval of Cmax,AUC0-216 and AUC0-∞ of test preparation was 91.8%-105.2%,97.8%-107.5% and 96.5%-108.8%,respectively.Conclusion: Domestic and imported letrozole preparations are bioequivalent.