摘要
羧酸酯酶(CES)是人和动物体内含量最丰富的水解酶,参与多种内源性和外源性化合物及药物的代谢过程。由于CES在人和动物体内的分布、活性具有明显的种属差异,这些差异与药物在人和不同种属动物体内的药代特性、药效及毒副作用密切相关,因此,本文就CES的分类、分布、诱导和抑制方面的种属差异,以及在血浆、肝、小肠、皮肤中的种属差异对酯类前药的代谢过程造成的影响进行总结,旨在为新药临床前研究正确选择实验动物提供参考,以准确预测临床药物代谢、药效和毒理作用。
Carboxylesterase(CES),the most abundant hydrolase in humans and animals,participates in the metabolism of various endogenous and exogenous compounds and drugs.The distribution and activity of CES have obvious species differences in hu mans and animals,which are closely related to the pharmacokinetics(PK),pharmacodynamics(PD)and toxic side effect of drugs.Therefore,this paper summarizes the effects of the difference in the classification,distribution,induction and inhibition of CES as well as the effects of species difference in plasma,liver,small intestine and skin on the metabolism of ester prodrugs,so as to provide a reference for the correct selection of experimental animals in preclinical studies of new drugs to accurately predict the clinical PK,PD and toxicological effects.
作者
邹小文
盛莉
李燕
ZOU Xiao-wen;SHENG Li;LI Yan(Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)
出处
《国际药学研究杂志》
CAS
北大核心
2020年第2期91-96,共6页
Journal of International Pharmaceutical Research
基金
中国医学科学院医学与健康科技创新工程经费资助项目(2017-I2M-1-010)。
关键词
羧酸酯酶
种属差异
药物代谢
药物研发
carboxylesterase
species difference
drug metabolism
drug discovery
