盐酸二甲双胍缓释片人体相对生物利用度及其药代动力学研究

Study on the Relative Bioavailability and Pharmacokinetics of Metformin Controlled-release Tablets in Human Volunteers

目的 :建立人血浆中盐酸二甲双胍的高效液相色谱测定方法 ,考察国产盐酸二甲双胍缓释片相对于普通片的生物等效性 ,并估算其药代动力学参数。方法 :血浆样品经 30 %HClO4沉淀蛋白后进行高效液相色谱分析。色谱柱为PhenomenexLunaC18(5 μm ,2 5 0mm× 4 6mm) ,流动相为乙腈 0 0 2 0mol/LNaH2 PO4(6 5∶35 ) ,流速为 1 0ml/min ,检测波长为 2 33nm。临床实验方案采用双交叉试验设计 ,2 0名受试者分两组服用缓释片和普通片。结果 :本方法绝对回收率大于 90 %。缓释片和普通片的主要药动学参数为 :单剂量时AUC0 2 4分别为9 13± 2 16和 9 5 3± 1 5 8μg·h/ml;cmax分别为 1 0 3± 0 2 8和 1 88± 0 2 9μg/ml;tmax分别为 4 0± 0 4和 2 4± 0 3h ;t1/ 2 分别为 6 6 1± 1 2 8和 3 95± 1 31h ;多剂量时AUCss分别为 11 73± 2 2 6和 5 84± 0 88μg·h/ml;cmax分别为1 15± 0 17和 1 17± 0 17μg/ml;cmin分别为 0 2 4± 0 11和 0 16± 0 12 μg/ml;cav分别为 0 4 9± 0 0 9和 0 5 1± 0 0 7μg/ml;tmax分别为 3 3± 0 6和 2 0± 0 3h ;AUC0 2 4和AUCSS经对数转换后方差分析和双单侧t检验 ,均无显著性差异。结论 :本方法简便准确。试验片和参比片吸收程度生物等效。盐酸二甲?

AIM:To establish a HPLC method for the study of bioavaibility and pharmacokinetics of metformin in human plasma. METHOD: A simple HPLC method using ultraviolet detection was developed, which entailed the direct injection of the plasma sample after deproteinating with 30% perchloric acid. The mobile phase consisted of 0.01M potassium dihydrogen orchophosphate(pH 4.0) and acetonitrile (65∶35, v/v ). Analysis was run at a flow-rate of 1.0 ml/min with the detector operated at wavelength 233nm. The mean absolute recovery value was above 90%, while the within-day and between-day coefficients of variation were less than 10%.The calibration curve was linear over a concentration range of 0.1 to 4.0 μg/ml. RESULT: The method was proved to be simple,sensitive and rapid.