【摘要】 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ρmax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~t(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:ρmin(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。ρmax经检验不具等效性,tmax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ρmax小、tmax有所延长,表明受试制剂具有缓释特性。更多还原

【Abstract】 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.更多还原