托莫西汀用于儿童ADHD个体化剂量调整的循证药学研究进展

Evidence-based pharmaceutical research progress of atomoxetine for individualized dose adjustment in childhood ADH

关键词:  托莫西汀，注意缺陷多动障碍，治疗药物监测，个体间变异，精准用药

Key words:  Atomoxetine, attention-deficit hyperactivity disorder, therapeutic drug monitoring, interindividual variation, precision medication

摘要:

目的 了解托莫西汀用于儿童期注意缺陷多动障碍（ADHD）个体化剂量调整的循证药学研究进展，为该药物的临床精准用药提供参考。方法 在PubMed数据库以“atomoxetine”（托莫西汀）、“therapeutic drug monitoring”（治疗药物监测）、“CYP2D6”、“children”（儿童）为关键词进行文献检索，检索时间从建库到2024年8月，纳入相关临床研究。制定支持临床实施托莫西汀治疗药物监测（TDM）的技术问题框架，对以往研究进行系统且全面的分析总结以回答框架问题。结果 当前证据显示，基于当前的体重给药方案时，托莫西汀血浆浓度存在显著的个体间变异。托莫西汀峰浓度是与其疗效相关的推荐监测参数，但与耐受性的相关性研究十分有限。结论 当前研究与支持临床上实施个体化剂量目标之间尚有差距，支持托莫西汀实施TDM的必要性证据尚有限，但累积的证据提示在ADHD患儿中实施TDM和CYP2D6基因分型可能是实现托莫西汀精准使用的发展方向，有助于提升合理用药水平。

Abstract:

OBJECTIVE To better understand the evidence-based pharmacological research progress on individualized dose adjustment of atomoxetine in children with attention deficit hyperactivity disorder (ADHD). METHODS We conducted a search on the PubMed database using the keywords "atomoxetine," "therapeutic drug monitoring (TDM)" "CYP2D6," and "children" to retrieve relevant clinical studies. The search period spaned from the inception of the database to August 2024. We design a technical framework to evaluate the clinical implementation of TDM for atomoxetine, conduct a systematic and comprehensive analysis of previous studies, and to summarize the findings to address the framework questions. RESULTS Current evidence showed significant variability in atomoxetine plasma concentrations among individuals. While peak concentration of atomoxetine was a key monitoring parameter linked to its effectiveness, research on its correlation with tolerability was very limited. CONCLUSION There is currently a gap between research and support for implementing individualized dose targets in clinical practice. While the evidence supporting the necessity of TDM for atomoxetine is limited, accumulating evidence suggests that implementing TDM and CYP2D6 genotyping in children with ADHD could be a way to achieve precise use of atomoxetine, thereby improving the level of rational drug utilization.