二甲双胍在小鼠体内的药动学研究

目的测定小鼠血浆中二甲双胍的浓度，并进行小鼠体内的药动学研究。方法小鼠灌胃给予盐酸二甲双胍（200、400、800mg／kg）并在0、0．33、0．67、1、2、3、4、6．8、10h共10个时间点采集血样（每个时间点小鼠3只），用HPLC法测定血浆样品中二甲双胍的浓度。结果二甲双胍在2～100mg／l的范围内呈线性关系；定量下限为2mg／L；低、中、高三种浓度加标回收率（％）分别为（93．4±2．7）、（87．3±1．9）、（86．4±1．7）；日内RSD〈5．2％，日间RSD〈5．4％。二甲双胍在小鼠体内的血药浓度一时间曲线符合二室模型。主要药动学参数：三个剂量的AUC分别为（52．93±2．34）、（112．49±8．88）、（136．88±7．16）h／l；CL分别为（0．059±0．002）、（0．063±0．004）、（0．093±0．004）1／h；t1／2分别为（3．61±0．22）、（2．83±0．23）、（3．12±0．16）h；tmax均为0．67h；Cmac分别为（18．61±0．78）、（42．77±1．05）、（39．32±0．33）mg／l。结论该法简便、准确、灵敏，可用于二甲双胍药动学研究。

Pharmacokinetics of Metformin in Mice

Objective To develop a method for the determination of mefformin in mice plasma and to investigate pharmacokinetics in mice. Method After ig administration of metformin hydrochloride with three doses of 200,400,800 mg/kg, the plasma samples from the mice （n = 3 ） were taken at 0,0. 33,0. 67,1,2,3,4, 6,8, and 10 h for the determination of the concentra-tion of metformin in mice blood by HPLC. Results Linearity was held in the range of 2 - 100 mg/L of melamin, the detection limit of the method was found to be 2 mg/ L. Values of recovery（ % ） obtained by standard addition method at 3 different concentration level were in the range of 93.4 ± 2. 7,87.3 ±1.9,86.4 ± 1.7 ,respectively; Inter-day RSD was less than 5.2 %, and Intra -day RSD was less than 5.4 %. The main pharmacokinetic parameters were as follows：AUC（52. 93 ± 2. 34）, （ 112.49 ± 8.88）, （136. 88 ± 7.16）h/L;CL（0. 059 ± 0. 002）, （0. 063 ± 0. 004）, （0. 093 ± 0. 004）1/ h;t1/2（3.61 ± 0.22）,（2.83 ± 0.23）,（3.12 ± 0.16）h;tmax0.67 h;Cmax（18.61 ± 0.78）,（42.77 ± 1.05 ）, （ 39. 32 ± 0. 33 ） mg/l. Conclusion The plasma concentration-time curve of mefformin fulfills the two compartment model. The method is accurate, sensitive, and rapid, and can be used in the studies of pharmaeokinetics of mefform.