Identification of the metabolite and cytochrome P450 isoforms involved in rat liver microsomal metabolism of TM208  

TM208在大鼠肝微粒体中代谢产物与细胞色素P450亚型代谢酶鉴别研究(英文)

作　　者：孔德涛[1] 凌笑梅[1] 韩方斌[1] 龚京莉[1] 葛泽梅[1] 李润涛[1] 崔景荣[2] 

机构地区：[1]北京大学药学院化学生物学系,北京100083 [2]北京大学天然药物及仿生药物国家重点实验室,北京100083

出　　处：《Journal of Chinese Pharmaceutical Sciences》2008年第1期30-34,共5页中国药学（英文版）

基　　金：National Basic Research Program of China (863 Program,Grant No.2004AA2Z3783);National Natural Science Foundation of China (Grant No.20672009)

摘　　要：To identify the metabolite and CYP450 isoforms involved in rat liver microsomal metabolism of TM208. The present study investigated the metabolism of TM208 and the effects of selective CYP450 inhibitors on the metabolism of TM208 in rat liver microsomes. Various specific inhibitors of CYP were used to identify the isoforms of CYP involved in the metabolism of TM208. The inhibitor of CYP2D and that of CYP2B had strong inhibitory effects on TM208 metabolism in a concentration-de- pendant manner, the inhibitor of CYP1A had a modest inhibitory effect, and the inhibitor of CYP3A seemed not to have an obvious inhibitory effect on TM208 metabolism. TM208 might mainly be metabolized by CYP2D and CYP2B in rat liver microsomes.在大鼠肝微粒体的体外代谢中研究作用于TM208的细胞色素P450亚型代谢酶。以不含细胞色素P450化学抑制剂的样品为对照,研究不同细胞色素P450亚型选择性化学抑制剂对TM208代谢转化率的影响。CYP2D和CYP2B的选择性抑制剂对TM208的代谢表现出浓度依赖性较强抑制作用,CYP1A的选择性抑制剂对TM208的代谢表现出一定抑制作用。CYP3A的选择性抑制剂对TM208的代谢没有表现出明显的抑制作用。TM208在大鼠肝微粒体体外代谢中主要通过CYP2D和CYP2B两种细胞色素P450亚型代谢酶参与代谢。

关 键 词：TM208 Rat liver microsomes METABOLISM Cytochrome P450 isoform 

分 类 号：R96[医药卫生—药理学]