托莫西汀在注意力缺陷多动障碍患儿中的精准药学研究:CYP2D6基因检测和治疗药物监测

A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder:CYP2D6 genetic testing and therapeutic drug monitoring

托莫西汀是第一种用于治疗儿童和成人注意力缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)的非兴奋剂药物,其安全性和有效性在儿科人群中表现出显著的差异性。该文首先从托莫西汀主要代谢酶CYP2D6基因多态性方面综述了影响托莫西汀药代动力学的遗传因素。同时,从治疗药物监测角度,总结了已有研究提出的托莫西汀在ADHD患儿中的有效浓度参考范围。总体而言,托莫西汀血药浓度峰值与临床疗效之间存在相关性,但缺乏中国儿童人群数据。因此,建立托莫西汀暴露的临床相关指标,定义中国ADHD患儿的有效治疗范围,结合CYP2D6基因分型,为托莫西汀的精准用药提供支持十分必要。

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder(ADHD),and its safety and efficacy show significant differences in the pediatric population.This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine,and then from the perspective of therapeutic drug monitoring,this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies.In general,there is an association between the peak plasma concentration of atomoxetine and clinical efficacy,but with a lack of data from the Chinese pediatric population.Therefore,it is necessary to establish related clinical indicators for atomoxetine exposure,define the therapeutic exposure range of children with ADHD in China,and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.