复方格列吡嗪片人体生物利用度及生物等效性研究

Relative Bioavailability and Bioequivalence of Compound Glipizide in Healthy Volunteers

目的研究复方格列吡嗪片人体生物利用度及生物等效性。方法单剂量给予国产的复方格列吡嗪片505mg(试验制剂)和格列吡嗪片5 mg(参比制剂)、盐酸二甲双胍片500 mg(参比制剂)。用高效液相色谱法测定血药浓度。用DAS程序计算相对生物利用度并评价两种制剂的生物等效性。结果口服试验制剂和参比制剂后,血浆中的格列吡嗪的Cmax分别为(406.72±68.10)ng/ml和(468.95±107.61)ng/ml;Tmax分别为(2.22±0.75)h和(1.98±0.91)h;AUC(0-24)分别为(2 812.26±897.73)(ng.h)/ml和(2 952.68±1 407.84)(ng.h)/ml;AUC(0-inf)分别为(3 034.67±1 245.72)(ng.h)/ml和(3 193.20±1 651.85)(ng.h)/ml。盐酸二甲双胍的Cmax分别为(1.15±0.25)μg/ml和(1.18±0.24)μg/ml;Tmax分别为(2.05±0.72)h和(2.08±0.94)h;AUC(0-24)分别为(5.77±1.62)(μg.h)/ml和(5.97±1.92)(μg.h)/ml;AUC(0-inf)分别为(6.38±1.98)(μg.h)/ml和(6.62±2.61)(μg.h)/ml。结论试验制剂与参比制剂的格列吡嗪和盐酸二甲双胍人体相对生物利用度分别为(114.0±56.1)%和(103.5±31.0)%,两者具有生物学等效性。

Objective To study the relative bioavailability and bioequivalence of compound glipizide in healthy volunteers. Methods A single oral dose （5 mg of Glipizide and 500 mg of Metformin hydrochloride） was given to volunteers. The concentrations of Glipizide and Metformin hydrochloride in plasma were determined by HPLC. The pharmacokinetic parameters were calculated by DAS program. Results After a single dose, the results were as follows： Cmax was （406.72±68. 10） ng/ml and （468. 95±107.61） ng/ml; Tmax was （2.22±0.75） h and （1.98±0.91） h; AUC（0-24）was （2 812.26±897.73） （ng· h）/ml and （2 952.68±1 407.84） （ng· h）/ml± AUC±0 i,o was （3 034.67±1 245.72） （ng· h）/mland （3 193.20±1 651.85） （ng· h）/ml for T and R respectively. The pharmaeokinetie parameters for Metformin hydroehloride were as follows： Cmax was （1.15± 0.25） μg/ml and （1.18±0.24） μg/ml± Tmax was （2.05±0.72） h and （2.08±0.94） h; AUC（0-24）was （5.77±1.62） （μg· h）/ ml and （5.97±1.92） （μg· h）/ml; AUC（0-inf） was （6.38±1.98） （μg· h）/ml and （6.62±2.61） （μg· h）/ml for T and R respectively. The relative bioavailability of Glipizide and Metformin hydroehloride was （114.0 ± 56.1）% and （103.5 ± 31.0）% respectively. Conclusion The results of the statistic analysis showed that the two formulations were hioequivalent.