盐酸二甲双胍缓释片人体相对生物利用度研究

Study on the relative bioavailability of metformin hydrochloride sustained-release tablets

目的:评价盐酸二甲双胍缓释片与普通片的人体相对生物利用度。方法:采用自身交叉试验设计,18名健康男性志愿者单剂量及多剂量口服盐酸二甲双胍普通片或缓释片,血药浓度采用HPLC-UV法测定。研究盐酸二甲双胍缓释片的相对生物利用度,并对缓释制剂的缓释情况进行评价。结果:盐酸二甲双胍缓释片和普通片单剂量给药后的Cmax分别为(0.779±0.368)和(1.189±0.528)μg/mL;Tmax分别为(2.67±1.26)和(1.56±0.56)h;AUC0→t分别为(7.176±3.134)和(7.006±3.016)μg.h.mL-1。盐酸二甲双胍缓释片的相对生物利用度为(103.38±14.68)%。盐酸二甲双胍缓释片和普通片多次给药后的Cmax分别为(0.783±0.192)和(1.037±0.281)μg/mL;Tmax分别为(3.12±0.58)和(1.56±0.29)h;AUC0→t分别为(6.585±1.647)和(4.158±1.033)μg.h.mL-1;波动度DF分别为(2.71±0.68)%和(2.79±0.56)%。结论:盐酸二甲双胍缓释片(每片含盐酸二甲双胍500 mg)每天1次口服与等剂量市售盐酸二甲双胍普通片每天2次口服具有生物等效性。

Objective：To study the relative bioavailability and pharmacokinetics of meffonnin hydrochlorlde sustained-release tablets. Methods： Single and multi-dose of mefformin hydrochloride tablets and sustained-release tablets were given to 18 male volunteers in a random cress-over design. Plasma samples were obtained and were determined by HPLC with UV detector, and then the bioavailability and pharmaeokineties of the two drugs were studied. Results： After the application of a 500mg single dose to volunteers, the pharmaeokineties parameters of mefformin hydrochloride tablets and sustained-release tablets were as follows： Cmax were （1.189 ± 0.528）μg/mL and （0.779 ± 0.368） μg/mL, Tmax were （1.56 ± 0.56） h and （2.67 ± 1.26）h; AUC0→1 were （7.006±3.016） pg＇h＇mL-1 and （7.176 ± 3.134）μg·h·mL^-1, respectively. The relative bioawilshility of the sustained-release tablets were （103.38 ± 14.68） % . After the application of multi-dose to volunteers, the pharmacokineties parameters were： Cmax were （0.783 ± 0. 192） and （1.037 ± 0.281）μg/mL; Tmax were （1.56 ± 0.29） h and （3.12 ± 0.58） h, AUC0→1, were （4.158 ± 1.033） μg·h·mL^-1 and （6.585 ± 1.647）μg·h·mL^-1 , DF were 2.79±0.56 and 2.71± 0.68. Conclusions： Mefformin hydrochloride tablets, when given 250 rag, twice a day, were as bioequivalanee as sustained-release tablets given 500 mg once a day.