基因多态性对阿米替林代谢动力学、药效学和不良反应的影响

doi:10.12092/j.issn.1009-2501.2019.02.019

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (2): 235-240.doi: 10.12092/j.issn.1009-2501.2019.02.019

• 综述与讲座 • 上一篇

基因多态性对阿米替林代谢动力学、药效学和不良反应的影响

王恩特^1,2，张晓丹¹，周双¹，赵侠^1,2，周颖^1,2, 崔一民^1,2

¹北京大学第一医院药剂科, 北京 100034；²北京大学药学院药事管理与临床药学系, 北京 100191

收稿日期:2018-09-03 修回日期:2018-12-17 出版日期:2019-02-26 发布日期:2019-03-04
通讯作者: 崔一民，男，主任药师，博士生导师，研究方向：临床药理学与临床药学。 Tel:010-66110802 E-mail:cui.pharm@pkufh.com
作者简介:王恩特，男，硕士研究生在读，研究方向：临床药学。 Tel:17718315025 E-mail:entenet@163.com
基金资助:
国家科技重大专项——重大新药创制“药物一致性评价关键技术与标准研究”（2017ZX09101001）

Effects of genetic polymorphisms on metabolic kinetics, pharmacodynamics and adverse reactions of amitriptyline

WANG Ente ^1,2, ZHANG Xiaodan ¹, ZHOU Shuang¹, ZHAO Xia ^1,2, ZHOU Ying ^1,2, CUI Yimin ^1,2

¹ First Hospital of Peking University, Beijing 100034, China; ²Peking University, Beijing 100191, China

Received:2018-09-03 Revised:2018-12-17 Online:2019-02-26 Published:2019-03-04

摘要/Abstract

摘要：

阿米替林是广泛应用于治疗重症抑郁症和创伤后应激障碍等多种精神疾病的三环类抗抑郁药。但在临床应用过程中发现，阿米替林的药物疗效存在较大个体差异，研究表明，CYP2D6、CYP2C19和ATP结合蛋白亚家族1抗体（ABCB1）等基因的多态性会影响阿米替林的药物代谢动力学(pharmacokinetics,PK)、药效学(pharmacodynamics,PD)和不良反应(adverse reactions,ADR)。在本文中，通过对比CYP2D6和CYP2C19的基因多态性对阿米替林PK、PD和ADR的影响，发现当CYP2C19为快代谢型或正常代谢型时，CYP2D6的基因多态性对阿米替林总体代谢的影响更大，而CYP2C19为慢代谢型时，CYP2C19的基因多态性影响更大。该结论为阿米替林基于基因多态性的个体化给药提供了建议与证据支持。

关键词: 阿米替林, 基因多态性, CYP2C19, CYP2D6, ATP结合蛋白亚家族1抗体

Abstract:

Amitriptyline is a tricyclic antidepressant for the treatment of severe depression, post-traumatic stress disorder and other psychiatric diseases, which is widely used in clinical application. However, there are significant individual differences in the response of amitriptyline. Research has shown that genetics polymorphisms of CYP2D6, CYP2C19 and ABCB1 have certain effects on the pharmacokinetics (PK), pharmacodynamics (PD) and adverse reactions (ADR) of amitriptyline. In this paper, we have drawn a preliminary conclusion by comparing the effects of CYP2D6 and CYP2C19 gene polymorphisms on amitriptyline PK, PD and ADR. For CYP2C19 ultrarapid metabolizers or extensive metabolizers, the genetic polymorphism of CYP2D6 has a greater effect on the overall metabolism of amitriptyline. However, for CYP2C19 poor metabolizers, the genetic polymorphisms of CYP2C19 have greater influence. Hopefully, this article can provide genetic-based advice and assistance for the individualized administration of amitriptyline.

Key words: amitriptyline, gene polymorphism, CYP2C19, CYP2D6, ABCB1

中图分类号:

R969.1
R971

王恩特，张晓丹，周双，赵侠，周颖, 崔一民. 基因多态性对阿米替林代谢动力学、药效学和不良反应的影响[J]. 中国临床药理学与治疗学, 2019, 24(2): 235-240.

WANG Ente, ZHANG Xiaodan, ZHOU Shuang, ZHAO Xia, ZHOU Ying, CUI Yimin. Effects of genetic polymorphisms on metabolic kinetics, pharmacodynamics and adverse reactions of amitriptyline[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(2): 235-240.

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基因多态性对阿米替林代谢动力学、药效学和不良反应的影响

Effects of genetic polymorphisms on metabolic kinetics, pharmacodynamics and adverse reactions of amitriptyline

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