【摘要】 目的研究复方格列本脲片在健康人体内的药物动力学及评价复方格列本脲片相对于格列本脲片与二甲双胍片联用是否具有生物等效性。方法采用随机自身交叉双周期设计方法,将18名健康男性受试者随机分为2组,分别单次交叉口服等剂量供试制剂或参比制剂(格列本脲2.5 mg,二甲双胍500 mg)后,采用HPLC法测定不同时间点的血药浓度,计算其主要药物动力学参数,评价两制剂的生物等效性。结果供试制剂和参比制剂格列本脲AUC0~10分别为(150.13±54.64)ng.h.mL-1和(158.85±59.15)ng.h.mL-1,cmax分别为(46.23±14.29)ng.mL-1和(44.16±15.16)ng.mL-1,tmax分别为(2.40±0.30)h和(2.40±0.30)h,t1/2分别为(1.73±0.71)h和(1.70±0.49)h。供试制剂和参比制剂二甲双胍AUC0~12分别为(7.79±2.17)μg.h.mL-1和(8.11±2.06)μg.h.mL-1,cmax分别为(1.47±0.44)μg.mL-1和(1.54±0.43)μg.mL-1,tmax分别为(2.10±0.50)h和(2.00±0.70)h,t1/2分别为(2.93±0.44)h和(2.83±0.48)h。上述结果经统计学分析无显著性差异(P>0.05)。供试制剂中格列本脲和二甲双胍相对于参比制剂的生物利用度分别为(96.4%±15.8%)和(96.9%±16.2%)。结论单剂量口服复方格列本脲片与口服相当剂量的格列本脲片和二甲双胍片具有生物等效性。更多还原

【Abstract】 OBJECTIVE To study the pharmacokinetics and bioequivalence of fixed-tablet glibenclamide/metformin in healthy volunteers.METHODS Eighteen volunteers were randomly divided into 2 groups.A single oral dose of test or reference tablets （glibenclamide 2.5 mg,metformin 500 mg） was given to each volunteer in an open crossover test.Glibenclamide/metformin plasma concentration was determined by HPLC.RESULTS The pharmacokinetic parameters of test and reference glibenclamide were as follows: AUC_0～10 was（150.13±54.64）ng·h·mL^-1 and（158.85±59.15）ng·h·mL^-1,c_max was（46.23±14.29）ng·mL^-1 and（44.16±15.16）ng·mL^-1,t_max was（2.40±0.30）h and（2.40±0.30）h,t_1/2 was（1.73±0.71）h and（1.70±0.49）h,respectively.The relative bioavailability was 96.4%±15.8%.The pharmacokinetic parameters of test and reference metformin were as follows: AUC_0～12 was（7.79±2.17）μg·h·mL^-1 and（8.11±2.06）μg·h·mL^-1,c_max was（1.47±0.44）μg· mL^-1 and（1.54±0.43）μg·mL^-1,t_max was（2.10±0.50）h and（2.00±0.70）h,t_1/2 were（2.93±0.44）h and（2.83±0.48）h,respectively.The relative bioavailability was 96.9%±16.2%.The main pharmacokinetic parameters showed no statistically significant difference between fixed-tablet glibenclamide/metformin and reference metformin tablet coadministered with glibenclamide tablet.CONCLUSIONS\ A single oral dose of fixed-tablet glibenclamide/metformin was bioequivalent with the same dose of glibenclamide and metformin.更多还原