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泰国及其他人群中影响自闭症谱系障碍药物反应的药物基因组学和非遗传因素:当前证据及未来意义

Pharmacogenomics and non-genetic factors affecting drug response in autism spectrum disorder in Thai and other populations: current evidence and future implications.

作者信息

Biswas Mohitosh, Vanwong Natchaya, Sukasem Chonlaphat

机构信息

Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.

Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Front Pharmacol. 2024 Feb 5;14:1285967. doi: 10.3389/fphar.2023.1285967. eCollection 2023.

Abstract

Autism spectrum disorder (ASD) may affect family and social life profoundly. Although there is no selective pharmacotherapy for ASD, the Food and Drug Administration (FDA) has recommended risperidone/aripiprazole to treat the associated symptoms of ASD, such as agitation/irritability. Strong associations of some pharmacokinetic/pharmacodynamic gene variants, e.g., and , with risperidone-induced hyperprolactinemia have been found in children with ASD, but such strong genetic associations have not been found directly for aripiprazole in ASD. In addition to pharmacogenomic (PGx) factors, drug-drug interactions (DDIs) and possibly cumulative effects of DDIs and PGx may affect the safety or effectiveness of risperidone/aripiprazole, which should be assessed in future clinical studies in children with ASD. Reimbursement, knowledge, and education of healthcare professionals are the key obstacles preventing the successful implementation of ASD pharmacogenomics into routine clinical practice. The preparation of national and international PGx-based dosing guidelines for risperidone/aripiprazole based on robust evidence may advance precision medicine for ASD.

摘要

自闭症谱系障碍(ASD)可能会对家庭和社会生活产生深远影响。尽管目前尚无针对ASD的选择性药物疗法,但美国食品药品监督管理局(FDA)已推荐使用利培酮/阿立哌唑来治疗ASD的相关症状,如激越/易激惹。在患有ASD的儿童中,已发现某些药代动力学/药效学基因变异(例如……和……)与利培酮引起的高泌乳素血症密切相关,但在ASD中尚未直接发现阿立哌唑存在如此强的基因关联。除了药物基因组学(PGx)因素外,药物相互作用(DDIs)以及DDIs和PGx的可能累积效应可能会影响利培酮/阿立哌唑的安全性或有效性,这应在未来针对患有ASD的儿童的临床研究中进行评估。医疗保健专业人员的报销、知识和教育是阻碍ASD药物基因组学成功应用于常规临床实践的关键障碍。基于有力证据制定国家和国际层面利培酮/阿立哌唑的基于PGx的给药指南可能会推动ASD的精准医学发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d1c/10875059/50f0cc3a7521/fphar-14-1285967-g001.jpg

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