盐酸二甲双胍/格列本脲复方胶囊的人体生物等效性及其药动学研究

Pharmacokinetics of glibenclamide/metformin hydrochloride combination

目的:建立人血浆中盐酸二甲双胍与格列本脲的HPLC测定法,评价盐酸二甲双胍/格列本脲复方胶囊相对于格列本脲片与盐酸二甲双胍片联合应用是否具有生物等效性。方法:20名健康受试者单剂量交叉口服等剂量供试制剂或参比制剂(格列本脲5mg和盐酸二甲双胍1000mg)后不同时间点采血,分别采用HPLC-UV,HPLC-MS检测法,测定血浆中盐酸二甲双胍及格列本脲的药物浓度,计算其药动学参数和相对生物利用度,评价两制剂的生物等效性。结果:供试制剂与参比制剂中盐酸二甲双胍AUC_(0-12)分别为(16.25±3.50)和(16.79±3.99)mg·h·L^(-1),C_(max)分别为(3.35±0.71)和(3.47±0.77)mg·L^(-1),T_(max)分别为(1.9±0.3)和(1.9±0.4)h,t_(1/2)ke分别为(2.81±0.31)和(2.79±0.33)h。供试制剂与参比制剂中格列本脲AUC_(0-15)分别为(1.236±0.523)和(1.170±0.522)mg·h·L^(-1),C_(max)分别为(0.258±0.075)和(0.264±0.073)mg·L^(-1),T_(max)分别为(2.5±0.4)和(2.4±0.4)h,t_(1/2)是e分别为(3.93±1.61)和(3.36±0.62)h。两制剂中盐酸二甲双胍及格列本脲主要药动学参数经统计学分析差异无显著性。结论:该方法简便灵敏,盐酸二甲双胍/格列本脲复方胶囊相对于格列本脲片与盐酸二甲双胍片联合应用具有生物等效性。

Objective: To evaluate whether compound capsules of glibenclamide/metformin hydrochloride (test) is bioequivalent to glibenclamide tablets (5mg) and metformin tablets (1000mg)combination (reference). Methods: Twenty healthy volunteers were randomly received with either a single crossover oral dose of test and reference capsules. The blood samples were collected from the volunteers at certain timepoints to measure the plasma drug concentration by HPLC-UV and HPLC-MS, respectively. The pharmacokinetic parameters and relative bioavailability were evaluated. Results: The pharmaeokinetics parameters of test and reference tablets for metformin were shown as AUC_(0-12)(16.25±3.50) vs (16.79±3.99)mg·h·L^(-1), C_(max)(3.35±0.71) vs (3.47±0.77)mg·L^(-1), T_(max)(1.9±0.3) vs (1.9±0.4) h, t_(1/2)ke (2.81±0.31) vs (2.79±0.33) h, and for glibenclamide AUC_(0-15) (1. 236±0. 523) vs (1. 170±0. 522)mg·h·L^(-1), C_(max)(0.258±0.075) vs (0.264±0.073)mg·L^(-1), T_(max) (2.5±0.4) vs (2.4±0.4) h, t_(1/2) ke (3.93±1.61) vs (3.36±0.62) h. No significant difference of the pharmacokinetic parameters between test and reference capsules was found. Conclusion: The compound capsules of glibenclamide/metformin hydroehloride are bioequivalent to glibenclamide/metformin hydrochloride tablets combination.