盐酸二甲双胍缓释胶囊在健康人体的生物等效性研究

Study on Pharmacokinetics and Relative Bioavailability of Metformin Hydrochloride Sustained Release Capsule in Healthy Volunteers

目的研究盐酸二甲双胍缓释胶囊的药动学和相对生物利用度。方法20名健康男性志愿者随机、交叉单剂量和多剂量口服盐酸二甲双胍缓释胶囊和普通片1000mg，采用高效液相色谱法测定其血药浓度，计算各药动学参数和相对生物利用度。结果20名健康志愿者单次po盐酸二甲双胍缓释片和普通片1000mg的主要药动学参数pmax分别为：（1．27±0．32）和（1．82±0．32）mg·L^-1；tmax分别为（5．0±1．62）和（2．95±0．72）h；AuC0～∞（13．53±3．87）和（12．36±2．24）mg·h·L^-1；AuC0～∞（14．44±4．09）和（12．66±2．34）mg·h·L^-1，相对生物利用度（F）为（109．62±26．81）％。多次po盐酸二甲双胍缓释胶囊和普通片的主要药动学参数分别为：pmax（0．10±0．05）和（0．33±0．09）mg·L^-1；AUCss（12．28±2．73）和（8．59±2．01）mg·h·L^-1；DF（239．68±30．98）％和（118．68±22．34）％，相对生物利用度（F）为（72．82±11．37）％。结论AUC经方差分析和双单侧t检验，两制荆具有生物等效性。pmax经检验不具等效性，tmax经非参数检验有显著性差异（P〈O．05），受试缓释胶囊较参比普通片的pmax、tmax有所延长，表明受试制剂具有缓释特性。

OBJECTIVE To study pharmacokinetics and relative bioavailability of mefformin hydroehloride sustained release capsule in healthy volunteers, METHODS The serum concentrations of 20 volunteers were determined by HPLC after a single and multiple oral doses of 1 000 mg of mefformin hydroehlofide capsule or reference mefformin hydrochloride tablet in a randomized crossover design study. The pharmacokinetic parameters were calculated and the relative bioavailability and bioequivalence of two formulations were evaluated. RESULTS The pharmacokinetic parameters for test and reference drugs after a single oral dose were as follows： pmax （ 1.27 ± 0.32） and （ 1.82 ± 0.32） mg· L^-1; toad（5.0 ± 1.62）and（2.95 ± 0.72）h; AUC0-∞ （13.53 ± 3.87）and （12.36.± 2.24） mg·h·L^-1 ;AUC0-∞ （14.44 ± 4.09） and （12.66 ± 2.34） mg·h·L^-1, respectively. The relative bioavailability of the test preparation was（ 109.62 ± 26.81 ） %. The pharmacokinetic parameters for test and reference preparations after multiple oral doses were as follows： pmin,（0.10 ± 0.05） and （0.33 ± 0.09）mg·L^-1; AUCss（ 12.28 ± 2.73） and （8.59 ± 2.01） mgmg·h·L^-1; DF（239.68 ± 30.98）% and （1118.68 ± 22.34）%. The relative bioavailability was（72.82 ± 11.37）%. CONCLUSION The Pmax of meffonnin sustained release capsules is lower and tmax is longer than those of regular ones. The results indicate that two formulations are bio-equivalent.