二甲双胍在小鼠体内的药动学研究 |
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引用本文: | 池晓峰,刘海日,赵辉,李发胜,刘茜.二甲双胍在小鼠体内的药动学研究[J].中国实用医药,2009,4(27):14-15. |
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作者姓名: | 池晓峰 刘海日 赵辉 李发胜 刘茜 |
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作者单位: | 1. 大连医科大学化学教研室,116044 2. 沈阳药科大学药分教研室 |
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摘 要: | 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。
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关 键 词: | 二甲双胍 高效液相色谱法 药动学 |
Pharmacokinetics of Metformin in Mice |
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Institution: | CHI Xiao-feng, LIU Hai-ri, ZHAO Hui, et al. (Department of Chemistry, Dalian Medical University, Dalian 116044, China) |
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Abstract: | 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. |
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Keywords: | Mefformin HPLC Pharmacokinetics |
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