盐酸二甲双胍缓释片人生物利用度和生物等效性  

Bioavailability and Bioequivalence of Sustained Release Tablets of Metformin Hydrochloride Compared with Its Regular Tablets in Healthy Volunteers

作　　者：朱定春[1] 朱余兵[1] 

机构地区：[1]南京医科大学附属南京第一医院药剂科,南京210006

出　　处：《中国药师》2007年第5期423-426,共4页China Pharmacist

摘　　要：目的:研究盐酸二甲双胍缓释片单次给药和多次给药的相对生物利用度及生物等效性。方法:采用随机双交叉实验设计,20名健康受试者单剂量口服受试制剂、参比制剂各1.0g及多剂量口服受试制剂(1.0g,bid)和参比制荆(500 mg,bid),用HPLC法测定血浆中的二甲双胍浓度,采用3p98软件计算药物动力学参数。结果:单剂量口服受试制剂、参比制剂1.0g后,普通片的C_(max)(1.95±0.31)mg·L^(-1)显著高于缓释片(1.51±0.27)mg·L^(-1),缓释片口服给药后,t_(max)为(3.4±0.8)h较普通片(1.6±0.3)h延迟(P<0.05),相对生物利用度为(114.6±8.1)%。多剂量口服给药后,缓释片在稳态时的C_(min)为(0.07±0.02)mg·L^(-1),C_(max)为(1.67±0.26)mg·L^(-1),而普通片分别为(0.15±0.05)mg·L^(-1),(1.21±0.22)mg·L^(-1)。结论:经统计学检验表明这两种制剂具有生物等效性,缓释片的达峰时间明显滞后于普通片,该缓释片显示出缓释特征。Objective： To investigate the relative bioavailability and bioequivalence of metformin hydrochloride sustained-release tablet. Method： A sensitive and rapid HPLC method was developed to determine the mefformin plasma concentration, single dose（ 1.0 g, qd） of reference and tested tablets, and multiple dose of reference （500 mg, bid） and tested （1.0 g, qd） tablets were orally administrated to twenty male healthy volunteers in randomized crossover design. The pharmacokinetics were calculated by 3p98 software. Result： The Cmax （ 1.95± 0.31 ） mg·L^-1 of tested tablet after single oral dose in 20 healthy volunteers was significantly higher than that （ 1.51 ± 0.27 ） mg·L^-1 of reference tablet. The tmax （ 3.4 ± 0.8 ） h of tested tablet was signifcantly longer than that （ 1.6 ±0.3 ） h of reference tablet（ P 〈 0.05 ）. The relative bioavailability of tested tablet was found to be（ 114.6 ± 8.1 ） %. The Cmin of tested and reference tablets at steady state were （ 0.07 ± 0.02） mg·L^-1 and （ 0. 15 ± 0.05 ） mg·L^-1, and the Cmax of tested and reference tablets were（ 1.67 ± 0.26 ）mg·L^-1 and（ 1.21 ± 0.22 ）mg·L^-1, respectively. Conclusion： Tested tablet of mefformin hydrochloride was bioequivalent to its reference tablet. Tested tablet exhibited a sustained-release property with a significantly longer tmax and a lower Cmax and a lower Cmax.

关 键 词：盐酸二甲双胍 缓释片 药物动力学 生物利用度 

分 类 号：R969[医药卫生—药理学]