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奥卡西平对阿立哌唑代谢可能的诱导作用:一例报告

Possible Oxcarbazepine Inductive Effects on Aripiprazole Metabolism: A Case Report.

作者信息

McGrane Ian R, Loveland Joshua G, de Leon Jose

机构信息

1 College of Health Professions & Biomedical Sciences, Department of Pharmacy Practice, The University of Montana, Missoula, MT, USA.

2 Department of Pharmacy, Shodair Children's Hospital, Helena, MT, USA.

出版信息

J Pharm Pract. 2018 Jun;31(3):361-363. doi: 10.1177/0897190017710523. Epub 2017 May 24.

Abstract

Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness. A limited number of reports are available which discuss reduced atypical antipsychotic concentrations secondary to oxcarbazepine CYP3A4 induction. We report a young boy taking oxcarbazepine (1200 mg/d) who presented with an unexpectedly low serum aripiprazole concentration. Utilizing therapeutic drug monitoring, pharmacogenetic testing, and a tool to evaluate drug-drug interactions, we estimate that oxcarbazepine possibly reduced his serum aripiprazole concentration by 68%. Our report is important, as it is the first to describe a drug-drug interaction between oxcarbazepine and aripiprazole. This report should encourage the completion of in vitro and clinical studies and the publication of case reports describing the possible inductive effects of oxcarbazepine on atypical antipsychotics (including cariprazine, lurasidone, quetiapine, aripiprazole, brexpiprazole, iloperidone, and risperidone) mediated by induction of the CYP3A4 metabolic pathway.

摘要

奥卡西平是一种细胞色素P450(CYP)3A4诱导剂,其结构与卡马西平相似。尽管未获得美国食品药品监督管理局的批准,但奥卡西平有时会被用于治疗患有自闭症谱系障碍(ASD)的青少年的攻击性行为。这些青少年可能还在服用第二代抗精神病药物,其中一些是CYP3A4代谢途径的底物。这些药物的联合使用可能会导致血清抗精神病药物浓度降低,从而可能降低疗效。目前仅有少数报告讨论了因奥卡西平诱导CYP3A4而导致非典型抗精神病药物浓度降低的情况。我们报告了一名服用奥卡西平(1200毫克/天)的小男孩,其血清阿立哌唑浓度意外偏低。通过治疗药物监测、药物遗传学检测以及一种评估药物相互作用的工具,我们估计奥卡西平可能使其血清阿立哌唑浓度降低了68%。我们的报告很重要,因为它首次描述了奥卡西平与阿立哌唑之间的药物相互作用。该报告应促使开展体外和临床研究,并发表病例报告,描述奥卡西平通过诱导CYP3A4代谢途径对非典型抗精神病药物(包括卡利拉嗪、鲁拉西酮、喹硫平、阿立哌唑、布雷哌唑、伊潘立酮和利培酮)可能产生的诱导作用。

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