盐酸二甲双胍缓释胶囊在健康人体的生物等效性研究

 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1 000 mg,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1 000 mg的主要药动学参数ρ_max分别为:(1.27±0.32)和(1.82±0.32)mg·L^-1;t_max分别为(5.0±1.62)和(2.95±0.72)h;AUC_0～t(13.53±3.87)和(12.36±2.24)mg·h·L^-1;AUC_0～∞(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:ρ_min(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,两制剂具有生物等效性。ρ_max经检验不具等效性,t_max经非参数检验有显著性差异(P<0.05),受试缓释胶囊较参比普通片的ρ_max小、t_max有所延长,表明受试制剂具有缓释特性。

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

OBJECTIVE To study pharmacokinetics and relative bioavailability of metformin hydrochloride 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 metformin hydrochloride capsule or reference metformin 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:ρ_max(1.27±0.32) and(1.82±0.32)mg·L^-1;t_max(5.0±1.62)and(2.95±0.72)h;AUC_0～t(13.53±3.87)and(12.36±2.24) mg·h·L^-1;AUC_0～∞(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:ρ_min(0.10±0.05) and(0.33±0.09)mg·L^-1;AUCss(12.28±2.73) and(8.59±2.01) mg·h·L^-1;DF(239.68±30.98)% and(118.68±22.34)%.The relative bioavailability was(72.82±11.37)%. CONCLUSION The ρ_max of metformin sustained release capsules is lower and t_max is longer than those of regular ones.The results indicate that two formulations are bio-equivalent.