盐酸二甲双胍在小鼠体内的药动学和组织分布

目的:研究盐酸二甲双胍在小鼠体内的药动学和组织分布。方法:小鼠灌胃给予盐酸二甲双胍200mg·kg-1,并在给药后0、0.33、0.67、1、2、3、4、6、8、10h共10个时间点采集血样和小肠、肾、肝、胃、肌肉、肺、脾、心脏组织样品(每个时间点小鼠3只),采用高效液相色谱法测定并计算血浆和各组织样品中二甲双胍的浓度。用DAS2.0软件计算药动学参数。结果:盐酸二甲双胍在小鼠体内的血药浓度-时间曲线符合二室模型;主要药动学参数AUC为(52.93±2.34)mg·h·L-1,CL为(0.059±0.002)L·h-1,t1/2为(3.61±0.22)h,tmax为0.67h,Cmax为(18.61±0.78)mg·L-1。在给药后0.67h,所有的组织中都能检测到二甲双胍;给药后10h,心、肝、脾、肺中已检测不到二甲双胍。各组织的AUC值从大到小排列依次为小肠、肾、胃、肝、肌肉、肺、心、脾。结论:盐酸二甲双胍进入小鼠体内后吸收及清除都较迅速,且在小鼠体内分布广泛,但在各组织分布情况显著不同。

Pharmacokinetics and Tissues Distribution of Metformin Hydrochloride in Mice

OBJECTIVE： To investigate the pharmacokinetics and tissue distribution of metformin hydrochloride in mice. METHODS： After administration of 200 mg·kg^-1 metformin hydrochloride （i.g.）, the blood samples and tissue samples were collected from mice （n=3） at 0, 0.33, 0.67, 1, 2, 3, 4, 6, 8 and 10 h in order to determine the concentration of metformin hydrochloride in plasma and tissues by HPLC. The pharmacokinetic parameters were calculated with DAS 2.0 software. RESULTS： The plasma concentration-time curves of metformin hydrochloride in mice were in line with two-compartment model. The main pharmacokinetic parameters were as follows： AUC（52.93 ± 2.34） mg·h·L^-1; CL（0.059 ± 0.002） L·h^-1; t1/2（3.61±0.22） h; tmax 0.67 h; Cmax（18.61±0.78） mg·L^-1. Metformin hydrochloride could be tested in all tissue samples at 0.67 h after administration but not be detected in heart, liver, spleen, lung at 10 h after administration. The AUC values of these tissues ranked in descending order of intestine, kidney, stomach, liver, muscle, lung, heart and spleen. CONCLUSION： Metformin hydrochloride can be abosorbed and cleared up rapidly in mice and it widely distributes in mice with different distribution points in those tissues.