托莫西汀用于儿童注意缺陷多动障碍个体化剂量调整的循证药学研究进展

郭宏丽; 黄剑; 徐欣; 吴丹丹; 刘倩琦; 陈峰

doi:10.13748/j.cnki.issn1007-7693.20242697

托莫西汀用于儿童注意缺陷多动障碍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 Attention Deficit Hyperactivity Disorder

摘要

摘要:
目的探讨托莫西汀用于儿童期注意缺陷多动障碍(attention deficit hyperactivity disorder，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”“therapeutic drug monitoring”“CYP2D6”“children”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(therapeutic drug monitoring，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，基于现有的体质量给药方案时，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，但支持托莫西汀实施TDM的必要性研究不断增加，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 explore the evidence-based pharmacological research progress on individualized dose adjustment of atomoxetine in children with attention deficit hyperactivity disorder(ADHD).
METHODS A search was conducted on the PubMed database using the keywords "atomoxetine" "therapeutic drug monitoring" "CYP2D6" and "children" to retrieve relevant clinical studies. The search period spaned from the inception of the database to August 2024. A technical framework was designed to evaluate the clinical implementation of therapeutic drug monitoring(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 can be a way to achieve precise use of atomoxetine, thereby improving the level of rational drug utilization.

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