二甲双胍在大鼠体内的药动学和组织分布  

Pharmacokinetics and tissues distribution of metformin in rats

作　　者：张桂春[1] 孙丽娟[1] 张凌红[1] 赵政[1] 

机构地区：[1]教育部和上海市脑功能基因组学重点实验室、华东师范大学脑功能基因组学研究所,上海200062

出　　处：《中国新药与临床杂志》2008年第3期202-206,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：上海市“浦江人才计划”资助项目(05PJ14044);上海市“登山行动计划”重大资助项目(06DZ19002)

摘　　要：目的研究二甲双胍在大鼠体内的药动学和组织分布。方法大鼠腹腔注射二甲双胍(100 mg·kg^(-1))并在0、10、20、30、60、120、240、480和720 min共9个时间点采集血样(大鼠共3只)和各组织样品(大鼠共27只,每个时间点3个),测定血浆和组织样品中的二甲双胍的浓度。结果AUC为(4 676±s 171)mg·min·L^(-1),CL为(21.4±0.8)mL·min^(-1)·kg^(-1),t(1/2)为(50±5)min,t_(max)为(20.0±1.0)min,c_(max)为(59±4)mg·L^(-1):给药后10 min,所有的组织中都能检测到二甲双胍,给药后12 h,肝脏、肺、脾脏和大脑中已检测不到二甲双胍。结论二甲双弧的血药浓度-时间曲线符合一室模型,在体内叹收快,兮布广泛,清除迅速,且可能主要是由肾脏清除;二甲双胍能够进入大脑。AIM To investigate the distribution and pharmacokinetic properties of metformin in rats. METHODS After a single administration （ip） of metformin with a dose of 100 mg·kg^-1, the plasma samples from the rats （n = 3） were taken at 0, 10, 20, 30, 60, 120, 240, 480, and 720 min for determination of the pharmacokinetic parameters of metformin in rat blood. The various organ samples were also taken from another group of animals （n = 27, 3 rats per time point） for the distribution study of the drug. RESULTS The main pharmacokinetic parameters were as follow： A UC （4 676 ＋ s 171 ） mg·min·L^-1, CL （21.4 ± 0.8） mL· min^-1·kg^-1, t1/2 （50 ± 5） min, tmax （20.0 ± 1.0） min, cmax （59 ± 4） mg·L^-1. Metformin were detected in all tissue samples 10 min after administration and could not be tested in liver, lung, spleen and brain 12 h after administration. CONCLUTION The plasma concentration-time curve of metformin revealed that the pharmacok- inetics of metformin in vivo fulfills the one-compartment model. The absorption, clearance with its diffuse distribution in vivo were rapid and the clearance appeared to be mainly via the kidney pathway. Metformin was readily permeable across the blood brain barrier.

关 键 词：二甲双弧 药动学 组织分布 色谱 高压液相 

分 类 号：R977.15[医药卫生—药品]