二甲双胍格列吡嗪片人体生物等效性研究

目的:评价二甲双胍格列吡嗪片复方制剂与两种单方制剂盐酸二甲双胍片和格列吡嗪片的生物等效性。方法:采用双周期自身交叉试验设计,24名健康男性受试者分别单剂量口服二甲双胍格列吡嗪片和盐酸二甲双胍片加格列吡嗪片,并于给药前及给药后不同时间点采集肘静脉血。采用高效液相色谱-质谱方法分别测定血浆中二甲双胍和格列吡嗪的浓度。结果:受试制剂与参比制剂中二甲双胍的Cmax分别为(1 470.75±441.55)和(1 618.63±554.58)μg.L-1,tmax分别为(2.79±1.37)和(2.63±1.24)h,t1/2分别为(5.80±1.38)和(6.24±1.14)h;AUC0-tn分别为(9 699.83±2 619.73)和(10 180.88±2 559.62)μg.h.L-1,AUC0-∞分别为(10 095.41±2 681.73)和(10 616.67±2 616.83)μg.h.L-1,受试制剂的相对生物利用度F0-tn、F0-∞分别为(97.18±23.26)%和(96.83±22.43)%;格列吡嗪的Cmax分别为(251.25±61.94)和(240.13±52.43)μg.L-1,tmax分别为(3.35±1.22)和(3.38±1.35)h,t1/2分别为(4.85±1.39)和(5.08±1.76)h;AUC0-tn分别为(1 561.44±475.73)和(1 588.82±507.40)μg.h.L-1,AUC0-∞分别为(1 664.13±580.08)和(1 704.93±647.89)μg.h.L-1,受试制剂的相对生物利用度F0-tn、F0-∞分别为(100.73±19.66)%和(100.59±19.70)%。结论:受试制剂和参比制剂具有生物等效性。

Bioequivalence of metformin-glipizide tablets in human

ABSTRACT] Objective： To study the bioequivalence of compound metformin-glipizide tablet （test preparation） and every single preparation （reference preparation）, metformin hydrochloride tablet and glipizide tablet, and evaluate the bioequivalence between the test preparation and the reference preparation. Methods： Serial venous blood samples were collected before and after the single oral dose of test preparation and reference preparation in 24 healthy male volunteers with a randomized two-period crossover method. The blood concentrations were determined by HPLC-MS/MS. Results： The main pharmacokinetic parameters of metformin in the test and reference preparation were as follows：Cmax were （1470.75±441.55）and （1618.63±554.58）μg·L-1,tmax were （2.79±1.37）and 2.63±1.24）h;t1/2 were （5.80±1.38） and （6.24±1.14）h;AUC0-tn were （9699.83±2619.73） and （10180.88±2559.62）μg·h·L^-1,AUC0-∞ were （10095.41±2681.73） and （10616.67±2616.83）μg·h·L-1,respectively. The data of glipizide in the test and reference preparation were as follows：（251.25±61.94） and （240.13±52.43）μg·-1,k were （3.35±1.22） and （3.38±1.35）h,t1/2 were （4.85±1.39）and （5.08±1.76）h;AUC0-tn were（1561.44±475.73） and （1588.82±507.40）μg·h·L-1,AUC0-∞ were （1664.13±580.08） and （1704.93±647.89）μg·h·L-1,Conclusion： The test preparation wasbioequivalent to the reference preparation.