CYP2D6基因多态性与托莫西汀治疗ADHD疗效的关联性研究进展

王玉文　周国岭　刘艳

[摘要] 托莫西汀是目前治疗ADHD的主要药物之一，主要经细胞色素P450酶代谢，是CYP2D6酶的底物。CYP2D6酶具有显著的基因多态性，不同个体CYP2D6酶对托莫西汀代谢能力有所差异，从而影响临床治疗ADHD的效果。查阅近年来国内外相关文献，对CYP2D6基因多态性与托莫西汀治疗ADHD疗效的关联性研究进展进行归纳总结。CYP2D6基因多态性可影响托莫西汀的疗效，CYP2D6慢代謝型患者需要更高的治疗剂量，发生不良反应的风险更高。CYP2D6基因型和表型对托莫西汀体内代谢和临床疗效的影响有待于进一步深入研究，ADHD患者CYP2D6基因多态性分布的全面系统调查也有待于开展，这将有利于托莫西汀治疗ADHD个体化用药的开展。

[关键词] CYP2D6；基因多态性；托莫西汀；ADHD

[中图分类号] R749 [文献标识码] A [文章编号] 1673-9701（2018）20-0165-04

Research progress of relationship between CYP2D6 gene polymorphism and therapeutic effect of tomoxetine in the treatment of ADHD

WANG Yuwen1 ZHOU Guoling2 LIU Yan2 SONG Mingfen3 LONG Sen1 SHI Jianfei4 WANG Zemin1

1.Department of Clinical Pharmacy， Hangzhou Seventh Peoples Hospital， Hangzhou 310013， China； 2.Department of Pediatric Psychology， Hangzhou Seventh Peoples Hospital， Hangzhou 310013， China； 3.Central Laboratory， Hangzhou Seventh Peoples Hospital， Hangzhou 310013， China； 4.Department of Psychiatry， Hangzhou Seventh Peoples Hospital， Hangzhou 310013， China

[Abstract] Tomoxetine is one of the main drugs for the treatment of ADHD， which is mainly matabolized by the cytochrome P450 enzyme， and is the substrate of CYP2D6 enzyme. CYP2D6 enzyme has a significant genetic polymorphism. Different CYP2D6 enzymes vary in their ability to metabolize tomoxetine， thereby affecting the clinical efficacy of ADHD. The related literature at home and abroad in recent years is retrieved， and the research progress of the association between CYP2D6 gene polymorphism and therapeutic effect of tomoxetine on ADHD is summarized. CYP2D6 gene polymorphism can affect the efficacy of tomoxetine， and the patients with slow metabolism of CYP2D6 need higher doses. The risk of adverse reactions is higher. The effect of CYP2D6 genotype and phenotype on the metabolism and clinical efficacy of tomoxetine remains to be further studied. A comprehensive and systematic investigation of the distribution of CYP2D6 polymorphism in ADHD patients remains to be carried out. This will be beneficial to the development of individualized dosage of tomoxetine in the treatment of ADHD.

[Key words] CYP2D6； Gene polymorphism； Tomoxetine； ADHD

注意缺陷与多动障碍（attention deficit and hyperactive disorder，ADHD）是儿童青少年时期常见的一种心理行为障碍，严重影响患者的学业和身心发展[1]。近年来，儿童ADHD发病率呈逐渐上升趋势，药物治疗一直是治疗ADHD的主要方法。托莫西汀是一个高特异性去甲肾上腺素再摄取抑制剂，可以有效治疗ADHD[2]，是目前临床治疗ADHD的主要药物。托莫西汀在人体内主要通过肝脏细胞色素P450酶代谢为活性代谢产物4-羟基托莫西汀。托莫西汀是CYP2D6酶的底物，因此其代谢速率主要受CYP2D6酶功能和活性的影响[3]。

CYP2D6是肝脏CYP450酶系的重要成员之一，约占肝药酶总量的2%～4%，却参与了近25%外源性药物的代谢[4]。CYP2D6酶具有显著的基因多态性，因此可导致不同个体CYP2D6酶对托莫西汀代谢能力有所差异，从而影响临床治疗ADHD的效果。……