葡萄糖醛酸转移酶(UGTs)诱导羧酸药物代谢激活的研究进展  

Advances in study of metabolic activation of carboxyl-acid containing drugs by UGTs

作　　者：谢彤[1] 梁艳[1] 郝海平[1] 谢林[1] 王广基[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室,江苏南京210009

出　　处：《药学学报》2009年第11期1193-1199,共7页Acta Pharmaceutica Sinica

摘　　要：含羧酸基团的药物可以通过葡萄糖醛酸转移酶的代谢转化,形成亲电子活性的酰基葡萄糖醛酸苷活性中间代谢产物,然后经过一系列的非酶或酶反应形成蛋白加合物或DNA加合物。加合物的形成是含羧酸基团药物形成特异质反应和基因毒性的主要因素。本文以该类药物的代谢激活为例,阐述了酰基葡萄糖醛酸苷的化学活性、致毒机制、分布特征以及产生的毒性反应,并探讨了研究现状和前景。The metabolic transformation of the drugs containing carboxylic acid groups can lead to the formation of acyl glucuronide metabolites through catalysis by glucuronosyltransferase, and produce pro-acyl glucuronide intermediate metabolites with electronic activity. Then, protein or DNA adducts appeared after a series of non-enzyme or enzyme reactions. These adducts would change the protein activity and potentially lead to idiosyncratic and genotoxicity. In this paper, we discussed the chemical activity, drug-induced mechanisms, distribution and toxicity resulting from this metabolic activation for these drugs, and stated the status and prospects of research in this field.

关 键 词：羧酸药物 葡萄糖醛酸转移酶 酰基葡萄糖醛酸苷 代谢激活 

分 类 号：R969[医药卫生—药理学]