氯苄律定在离体大鼠简易肝微粒体的代谢动力学

目的 测试氯苄律定（CPU-86017）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），分别加入不同尝试的CPU-86017，测定药物代谢速率，Vmax、Vm。结果 测出肝代谢t1/2为1h,Km为0.031mmol/L,Vmax为891pmol/Lmg蛋白/h。结论 肝内代谢速率较慢，可排除肝首过效应，亦未见肝本科饱和现象。

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

Objective It was intended to explore for the first time the metabolism of CPU 86017 in simplified preparation of liver microsome in rats. Methods The 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. Results The 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. Conclusion The 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.