论文部分内容阅读
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。
Objective To evaluate the relative bioavailability of domestic compound metformin hydrochloride capsules (test preparation) and metformin hydrochloride tablets in combination with glyburide (reference preparation). Methods Eighteen healthy male volunteers were randomized to receive oral administration of two test preparations (each containing metformin 250 mg and glibenclamide 1.25 mg) or a reference formulation of metformin hydrochloride tablets (250 mg) and glibenclamide tablets (2.5 mg) 1. The plasma concentration of metformin was determined by ion-pair high performance liquid chromatography (HPLC). The plasma concentration of glyburide was determined by HPLC-MS and the pharmacokinetic parameters were calculated. The relative bioavailability of the test formulation was evaluated. The main pharmacokinetic parameters of metformin were as follows: AUC0-24 were (5.90 ± 1.36) and (5.95 ± 1.35) μg · h · mL-1, respectively; AUC0- ∞ were (6.17 ± 1.36) and (6.28 ± 1.36) μg · h · mL-1, respectively, with Cmax of (0.82 ± 0.21) and (0.82 ± 0.14) μg · mL- (1.54 ± 0.98) h, the relative bioavailability was (100.21 ± 14.10)%. The main pharmacokinetic parameters of glyburide were as follows: AUC0-16 were (270.28 ± 61.82) and (268.70 ± 61.99) ng · (28.83 ± 61.97) and (284.17 ± 67.85) ng · h · mL-1, respectively, with Cmax of (62.83 ± 10.89) and (61.44 ± 12.11) ng · mL- tmax were (2.53 ± 0.79) and (2.81 ± 0.75) h, respectively. The relative bioavailability was (101.67 ± 14.54)%. Conclusions According to the statistical analysis, there is no significant difference between the main pharmacokinetic parameters of the test preparation and the reference preparation. The test preparation and the reference preparation are bioequivalent.