肝脏和小肠对药物首过代谢模型的研究进展

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (8): 944-949.

肝脏和小肠对药物首过代谢模型的研究进展

朱晶¹, 郭建军², 林俊辉², 卜海之², 陈西敬¹

¹中国药科大学药物代谢研究中心,南京 210008,江苏;
²苏州圣苏新药开发有限公司,苏州 215104,江苏

收稿日期:2012-04-06 修回日期:2012-06-05 出版日期:2012-08-26 发布日期:2012-08-14
通讯作者: 陈西敬,男,博士,教授,博士生导师,研究方向:药物代谢动力学。Tel: 025-83271286 E-mail: chenxi-lab@hotmail.com;卜海之,男,博士,研究方向:药物代谢动力学。Tel: 0512-67683276 E-mail: haizhi.bu@3dbiooptima.com
作者简介:朱晶,女,硕士研究生,研究方向:药物代谢动力学。Tel: 025-83271286 E-mail: zhujing-zjg@163.com
基金资助:
苏州科学技术局姑苏创新创业领军人才基金的资助(XG0826)

Research advances in models of hepatic and intestinal first-pass drug metabolism

ZHU Jing¹, GUO Jian-jun², LIN Jun-hui², BU Hai-zhi², CHEN Xi-jing¹

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu,China;
²3D BioOptima Co., Ltd., Suzhou 215104, Jiangsu,China

Received:2012-04-06 Revised:2012-06-05 Online:2012-08-26 Published:2012-08-14

摘要/Abstract

摘要： 肝、肠首过代谢有时是药物口服生物利用度低的主要原因之一。本文介绍了肝脏和小肠中药物代谢酶的分布、含量和催化活性,比较了两者在生理结构上的差异对首过代谢的影响,对有关研究方法,包括体外、原位、体内、体外-体内结合以及基因敲除和转基因模型等方面的进展进行了概述。

关键词: 首过代谢, 药物代谢酶, 肝脏, 小肠, 生物利用度

Abstract: Low oral bioavailability of a drug could be attributed to poor absorption and/or extensive first-pass metabolism.The liver and small intestine are the two most important organs for first-pass metabolism. In this review, the important drug-metabolizing enzymes located in the human liver and small intestine are introduced and the effects of different physiological structures of the two organs on overall first-pass metabolism are presented. Moreover, the research advances of the methods used to estimate hepatic and intestinal first-pass metabolism, such as in vitro, in situ, in vivo, in vitro-in vivo combined, knockout and transgenic models, are also summarized.

Key words: First-pass metabolism, Drug-metabolizing enzyme, Liver, Intestine, Bioavailability

中图分类号:

R969.1

朱晶, 郭建军, 林俊辉, 卜海之, 陈西敬. 肝脏和小肠对药物首过代谢模型的研究进展[J]. 中国临床药理学与治疗学, 2012, 17(8): 944-949.

ZHU Jing, GUO Jian-jun, LIN Jun-hui, BU Hai-zhi, CHEN Xi-jing. Research advances in models of hepatic and intestinal first-pass drug metabolism[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(8): 944-949.

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