盐酸二甲双胍肠溶片的药动学及生物等效性研究

目的:研究盐酸二甲双胍肠溶片的药动学和相对生物利用度,验证国产与进口盐酸二甲双胍肠溶片的生物等效性。方法:采用高效液相色谱法测定26名健康男性志愿者自身交叉单剂量口服国产与进口盐酸二甲双胍肠溶片1000mg后的经-时血药浓度,计算主要药动学参数以及国产制剂的相对生物利用度。结果:国产与进口盐酸二甲双胍肠溶片的药-时曲线符合一室模型,其主要药动学参数:Cmax分别为(84.9±16.4)、(84.5±13.8)μg.L-1,tmax分别为(0.67±0.07)、(0.77±0.08)h,t1/2ke分别为(1.90±0.17)、(1.79±0.19)h,AUC0～t分别为(161.9±16.8)、(157.2±19.7)μg.h.L-1,AUC0～∞分别为(179.7±18.2)、(173.4±19.2)μg.h.L-1。国产相对于进口盐酸二甲双胍肠溶片的生物利用度为(109.0±7.2)%。结论:国产与进口盐酸二甲双胍肠溶片生物等效。

Pharmacokinetics and Bioequivalence of Metformin Hydrochloride Enteric - coated Tablets

OBJECTIVE： To study the pharmacokinetics and relative bioavailability of metformin hydrochloride enteric-coated tablets and validate the bioequivalence between the domestic and the imported metformin hydrochloride enteric-coated tablets. METHODS： An oral single dose （1 000 mg） of domestic or imported metformin hydrochloride enteric-coated tablets was given to 26 healthy volunteers in a randomized crossover study. The time - concentrations of metformin hydrochloride were determined by HPLC. The pharmacokinetic parameters as well as relative bioavailability of the domestic tablets were computed. RESULTS： The concentration-time curves of the two kinds of metformin hydrochloride enteric-coated tablets were in line with one- compartment model. The main pharmacokinetic parameters of the domestic vs. the imported metformin hydroehloride enteric-coated tablets were as follows： Cmax（84.9± 16.4）μg·L^-1 vs.（84.5± 13.8）μg·L^-1; tmax（0.67± 0.07） h vs.（0.77±0.08） h; t1/2 Ke（1.90±0.17）h vs.（1.79±0.19） h; AUC0-t（161.9± 16.8）μg·h·L^-1 vs.（157.2± 19.7）μg·h·L^-1; AUC 0-∞ （179.7± 18.2） μg·h·L^-1 vs. （173.4_± 19.2）μg·h·L^-1. The relative bioavailability of the domestic enteric-coated tablets was （109.0 ± 7.2）% as against the imported enteric-coated tablets. CONCLUSION： The two kinds of tablets were bioequivalent.