【摘要】 目的评价国产的复方盐酸二甲双胍胶囊(试验制剂)与市售的盐酸二甲双胍片联合格列本脲片(参比制剂)的人体相对生物利用度。方法18名健康男性志愿者随机交叉口服试验制剂2粒(每粒含二甲双胍250mg,格列本脲1.25mg)或参比制剂盐酸二甲双胍片(250mg)2片、格列本脲片(2.5mg)1片。二甲双胍的血药浓度采用离子对高效液相色谱法(HPLC)测定,格列本脲的血药浓度采用高效液相色谱-质谱法(HPLC-MS)测定,计算两者的药动学参数并评价试验制剂的相对生物利用度。结果受试者单次服用试验制剂或参比制剂后,二甲双胍的主要药动学参数如下:AUC0-24分别为(5.90±1.36)和(5.95±1.35)μg·h·mL-1,AUC0-∞分别为(6.17±1.36)和(6.28±1.36)μg·h·mL-1,Cmax分别为(0.82±0.21)和(0.82±0.14)μg·mL-1,tmax分别为(1.43±0.88)和(1.54±0.98)h,相对生物利用度为(100.21±14.10)%;格列本脲的主要药动学参数如下:AUC0-16分别为(270.28±61.82)和(268.70±61.99)ng·h·mL-1,AUC0-∞分别为(287.13±61.97)和(284.17±67.85)ng·h·mL-1,Cmax分别为(62.83±10.89)和(61.44±12.11)ng·mL-1,tmax分别为(2.53±0.79)和(2.81±0.75)h,相对生物利用度为(101.67±14.54)%。结论经统计学分析,试验制剂与参比制剂的主要药动学参数之间差异无统计学意义,试验制剂与参比制剂生物等效。更多还原

【Abstract】 OBJECTIVE Investigate the bioavailability of domestic glyburide/metformin combination capsule in healthy male volunteers.METHODS A single oral dose of two test capsules of metformin hydrochloride / glibenclamide(250mg/1.25mg) versus equivalent doses of reference preparations of co-administered two metformin hydrochloride tablet(500mg) and one glibenclamide tablet(2.5mg) was given to 18 healthy male volunteers in a randomized crossover study. Plasma concentrations of metformin were determined by an ion-pair HPLC method with UV-detector and a HPLC/MS method for glibenclamide.RESULTS The main pharmacokinetics of metformin in test and reference were as follow: AUC_ 0-24 were:(5.90±1.36)μg·h·mL~ -1 and (5.95±1.35)μg·h·mL~ -1 ,AUC_ 0-∞ were:(6.17±1.36)μg·h·mL~ -1 and (6.28±1.36)μg·h·mL~ -1 ,C_ max were:(0.82±0.21)μg·mL~ -1 and~ (0.82±0.14)μg·mL~ -1 ,t_ max were:(1.43±0.88)h and (1.54±0.98)h,the relative bioavailability was (100.21±14.10)%;the main pharmacokinetics of glibenclamide of the test and reference were as follow:AUC_ 0-16 were:(270.28±61.82)ng·h·mL~ -1 and (268.70±61.99)ng·h·mL~ -1 ,AUC_ 0-∞ :(287.13±61.97)ng·h·mL~ -1 and (284.17±67.85)ng·h·mL~ -1 ,C_ max were:(62.83± 10.89 )ng·mL~ -1 and (61.44±12.11)ng·mL~ -1 ,t_ max were:(2.53±0.79)h and (2.81±0.75)h,the relative bioavailability was ( 101.67 ±14.54)%.CONCLUSION The result of statistical analysis showed that two formulations were bioequivalent.更多还原