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遗传药理学与儿童和青少年的奥卡西平:超越*15:02。

Pharmacogenetics and Oxcarbazepine in Children and Adolescents: Beyond *15:02.

机构信息

Division of Adolescent Medicine, Children's Mercy Kansas City, Kansas City, Missouri, USA.

Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, Missouri, USA.

出版信息

J Child Adolesc Psychopharmacol. 2024 Feb;34(1):61-66. doi: 10.1089/cap.2023.0064.

Abstract

Oxcarbazepine is thought to be better-tolerated and less susceptible to drug-drug interactions than its predecessor, carbamazepine. Genetic testing for *15:02 is recommended in specific populations to identify those at high risk of severe hypersensitivity reactions; however, other pharmacologic and pharmacogenetic factors that can impact drug disposition may be involved. We present a case of an 8-year-old boy treated with oxcarbazepine who developed drug reaction with eosinophilia and systemic symptoms (DRESS) with Stevens-Johnsons syndrome overlap and was negative for *15:02. We review the extant literature related to oxcarbazepine disposition, and potential pharmacogenetic variants in aldoketoreductase 1C ()2-4 that may contribute to this risk. Genetic variability in oxcarbazepine disposition pathways may contribute to tolerability and toxicity, including the development of hypersensitivity reactions. While preemptive genetic testing for *15:02 in individuals of Asian ancestry is recommended to prevent severe hypersensitivity reactions to oxcarbazepine, oxcarbazepine concentrations and variation may contribute to the risk of severe adverse reactions. We provide recommendations for future study to elucidate whether these individual factors are important for reducing the risk of severe adverse events.

摘要

奥卡西平被认为比其前体卡马西平更耐受,并且不易发生药物相互作用。建议在特定人群中进行 *15:02 的基因检测,以识别那些有严重过敏反应高风险的人群;然而,可能涉及其他影响药物处置的药理学和遗传药理学因素。我们报告了一例 8 岁男孩使用奥卡西平治疗,发生伴有 Stevens-Johnson 综合征重叠的药物反应伴嗜酸性粒细胞增多和全身症状(DRESS),且 15:02 为阴性。我们回顾了与奥卡西平处置相关的现有文献,以及醛酮还原酶 1C()2-4 中可能导致这种风险的潜在遗传变异。奥卡西平处置途径的遗传变异性可能导致耐受性和毒性,包括过敏反应的发展。虽然建议对亚洲血统的个体进行15:02 的预防性基因检测,以预防对奥卡西平的严重过敏反应,但奥卡西平的浓度和变异性可能会增加严重不良反应的风险。我们为未来的研究提供了建议,以阐明这些个体因素是否对降低严重不良事件的风险很重要。

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