中国临床药学杂志

目的比较4种盐酸二甲双胍缓释片在Beagle犬体内的生物等效性。方法采用单剂量随机四周期四交叉试验设计。8只Beagle犬分别灌胃给予4种盐酸二甲双胍缓释片(受试制剂A、B、D,参比制剂C)50 mg·kg^-1。于给药前及给药后不同时间点取血,采用HPLC法测定血浆中盐酸二甲双胍浓度,计算主要药动学参数,并评价各受试制剂的相对生物利用度和生物等效性。结果受试制剂D、A、B和参比制剂C的主要药动学参数为:t_max(2.6±1.2)、(2.1±0.9)、(2.1±0.6)和(2.7±0.5)h,ρ_max(8 881.7±2 575.1)、(9 587.5±2 072.0)、(8 189.3±2 013.8)和(8 579.3±1 691.9)μg·L^-1,t_1/2(4.4±0.6)、(4.6±0.4)、(4.7±1.3)和(4.2±1.0)h,AUC_0→1(61 378.8±18 731.0)、(56 602.8±10 737.8)、(46 766.1±9 515.0)和(56 754.2±12 384.2)μg·h·L^-1,AUC_0→∞(62 863.1±19 047.8)、(57 975.5±11 186.1)、(48 185.2±9 815.1)和(58 372.7±13 672.0)μg·h·L^-1,MRT(0.16±0.01)、(0.17±0.01)、(0.19±0.05)和(0.17±0.02)h。受试制剂D、A、B的相对生物利用度分别为(118.0±61.4)%、(107.0±42.0)%和(91.4±12.2)%。结论3种受试制剂和参比制剂C生物等效,其中受试制剂D的生物利用度最高,其次是A、B。

AIM To evaluate the bioequivalence of four metformin hydrochloride sustained release tablets in Beagle dogs.METHODS A randomized single-dose cross-over design was used to evaluate the bioequivalence of four metformin hydrochloride sustained release tablets(test preparations A,B,D and reference prearation C) in eight Beagle dogs.The drug concentration of metformin hydrochloride in plasma was determined by HPLC.RESULTS The main pharmacokinetic parameters of test preparations D,A,B and reference preparation C were as follows:t_max(2.6±1.2),(2.1±0.9),(2.1±0.6) and(2.7±0.5) h;ρ_max(8 881.7±2 575.1),(9 587.5 ±2 072.0),(8 189.3 ±2 013.8) and(8 579.3 ±1 691.9)μg·L^-1;t_1/2(4.4 ±0.6),(4.6 ±0.4),(4.7 ± 1.3) and(4.2 ± 1.0) h;AUC_0→1(61 378.8 ±18 731.0),(56 602.8 ± 10 737.8),(46 766.1 ± 9 515.0) and(56 754.2± 12 384.2) μg·h·L^-1;AUC_0→∞(62 863.1 ±19 047.8),(57 975.5 ±11 186.1),(48 185.2 ±9 815.1) and(58 372.7 ± 13 672.0)μg·h·L^-1;MRT(0.16 ±0.01),(0.17±0.01),(0.19±0.05) and(0.17 ±0.02) h.The relative bioavailability of metformin hydrochloride in test preparations D,A,B was(118.0 ± 61.4)%,(107.0±42.0)%and(91.4± 12.2)%,respectively.CONCLUSION Three test preparations and reference preparation C are bioequivalent while test preparation D has the highest relative bioavailability followed by A and B.