氯苄律定在离体大鼠简易肝微粒体的代谢动力学

The Rate and Kinetics of CPU 86017 Metabolism in Simplified Rat Liver Microsome

目的 测试氯苄律定 (CPU 86 0 17)在离体大鼠肝简易微粒体中的代谢。方法 首先制备肝简易微粒体 (含肝细胞胞浆及部分线粒体 ) ,分别加入不同浓度的CPU 86 0 17,测定药物代谢速率、Vmax、Km。结果 测出肝代谢t1/ 2 为 1h ,Km为 0 0 31mmol/L ,Vmax为 891pmol/mg蛋白 /h。结论 肝内代谢速率较慢 ,可排除肝首过效应 ,亦未见肝酶饱和现象。

ObjectiveIt was intended to explore for the first time the metabolism of CPU 86017 in simplified preparation of liver microsome in rats. MethodsThe simplified rat liver microsome was prepared and the metabolism of CPU 86017 was conducted by adding varying concentrations in the oxygen saturated microsome preparation and the metabolizing rate, V max and K m were measured. ResultsThe t 1/2 of CPU 86017 by hepatic metabolism was 1 h. The K m and V max were 0.031 mmol/L and 891 pmol/mg protein/h, respectively. ConclusionThe metabolizing rate in the rat lever was slow, therefore, the low bioavailability of the compound is not attributed by the first pass metabolism in liver, and the saturation phenomena of the drug enzyme was also not found.