内源性物质代谢对药物代谢处置的影响及机制研究

doi:10.12092/j.issn.1009-2501.2019.05.016

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (5): 580-588.doi: 10.12092/j.issn.1009-2501.2019.05.016

内源性物质代谢对药物代谢处置的影响及机制研究

陈泓竹¹，刘建明²，周芳¹，贾元威³，王广基¹，张经纬¹

¹中国药科大学药物代谢动力学重点实验室，南京 210009，江苏；²江西医学高等专科学校，上饶 334000，江西；³皖南医学院弋矶山医院临床药学部，安徽省药物临床评价中心，芜湖 241001，安徽

收稿日期:2019-01-15 修回日期:2019-04-02 出版日期:2019-05-26 发布日期:2019-05-28
通讯作者: 张经纬，男，副研究员，研究方向：药物代谢动力学 Tel：025-83271176 E-mail：zhangjw_cnnj@sina.com
作者简介:陈泓竹，女，硕士研究生，研究方向：药物代谢动力学。 Tel：15298363005 E-mail：chenhz512@126.com
基金资助:
国家自然科学基金（81573494，81803625，81573496）；江苏省自然科学基金（BK20160076，BK20180558）

Effect and mechanism of endogenous metabolism on drug metabolism and disposition

CHEN Hongzhu¹, LIU Jianming², ZHOU Fang¹, JIA Yuanwei³, WANG Guangji¹, ZHANG Jingwei¹

¹Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu, China; ²Jiangxi Medical College, Shangrao 334000, Jiangxi, China; ³Anhui Provincial Drug Clinical Evaluation Center, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui, China

Received:2019-01-15 Revised:2019-04-02 Online:2019-05-26 Published:2019-05-28

摘要/Abstract

摘要：

内源性物质代谢是机体在细胞、分子等水平上对内外因素的应答过程，是机体自有成分对生理、疾病及外源物质作用的反馈。药物代谢处置是药物发挥药效和产生不良反应的前提。不同生理或疾病状态下，内源性物质代谢发生改变势必影响药物代谢处置，进而影响药效及不良反应。国内外研究表明，内源性物质代谢变化，可导致代谢通路中某些中间产物或终产物的含量改变，从而引起药物代谢酶和转运体的变化。本文就内源性糖代谢、脂代谢、核苷酸代谢、氨基酸代谢及激素等对药物代谢处置的影响及其机制进行综述，以期为不同生理及疾病状态下的临床安全用药和个体化治疗提供借鉴和思路。

关键词: 内源性物质代谢, 药物代谢酶, 转运体, 临床安全用药

Abstract:

Endogenous substance metabolism is the response process of the body to internal and external factors at the level of cells, molecules, etc. It is the feedback of the body's own components on health, disease and foreign substances. Drug metabolism and disposition is a prerequisite for drugs to exert their effects and produce adverse reactions. Under different physiological or disease states, changes in the metabolism of endogenous substances will inevitably affect the drug metabolism, which will affect the efficacy and adverse reactions. Studies at home and abroad have shown that changes in the metabolism of endogenous substances can lead to changes in the content of certain intermediates or end products in the metabolic pathway, leading to changes in drug metabolizing enzymes and transporters. This article reviews the effects of endogenous glucose metabolism, lipid metabolism, nucleotide metabolism, amino acid metabolism and hormones on drug metabolism and its mechanisms, in order to provide reference and ideas for clinical safe medication and individualized treatment under different physiological and disease states.

Key words: endogenous substance metabolism, drug metabolism enzyme, transporter, clinical safe medication

中图分类号:

R969.1

陈泓竹，刘建明，周芳，贾元威，王广基，张经纬. 内源性物质代谢对药物代谢处置的影响及机制研究[J]. 中国临床药理学与治疗学, 2019, 24(5): 580-588.

CHEN Hongzhu, LIU Jianming, ZHOU Fang, JIA Yuanwei, WANG Guangji, ZHANG Jingwei. Effect and mechanism of endogenous metabolism on drug metabolism and disposition[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(5): 580-588.

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内源性物质代谢对药物代谢处置的影响及机制研究

Effect and mechanism of endogenous metabolism on drug metabolism and disposition

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