Pharmacogenetics of Carbamazepine: A Systematic Review on CYP3A4 and CYP3A5 Polymorphisms.

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI:10.2174/0118715273298953240529100325

Rachda Riffi, Wefa Boughrara, Amina Chentouf, Wassila Ilias, Narimene Malika Taieb Brahim, Amel Alioua Berrebbah, Fatma Belhoucine

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Abstract

Background and objective: The association between carbamazepine (CBZ) metabolism and resistance in epilepsy and the genetic polymorphisms of CYP3A5 (rs776746 and rs15524) and CYP3A4 (rs2242480, rs2740574, rs35599367, rs12721627, and rs28371759) has been the subject of previous investigations with controversial results. Hence, we conducted a systematic review to assess the potential link between these polymorphisms and CBZ metabolism and resistance.

Methods: Identifying relevant studies was carried out by searching PubMed, Scopus, PharmGKB, EPIGAD, and PHARMAADME databases up until June 2023. The studies included in our analysis investigated the connection between CYP3A5 (rs776746 and rs15524) and CYP3A4 (rs2242480, rs2740574, rs35599367, rs12721627, and rs28371759) polymorphisms and CBZ metabolism and resistance.

Results: This review included a total of 23 studies and more than 2177 epilepsy patients. It was found that the CYP3A4 (rs12721627 and rs28371759) polymorphisms are associated with reduced catalytic activity, whereas the CYP3A4 (rs2740574) polymorphism is linked to lower levels of CBZ-diol and decreased activity. It was also observed that the CYP3A5 (rs776746) polymorphism influences the dose-adjusted plasma levels of CBZ.

Conclusion: Although these findings highlight the impact of genetic variations in the CYP3A4 and CYP3A5 genes on CBZ pharmacokinetics and pharmacodynamics, further studies across diverse populations are essential to enhance personalized epilepsy therapy in clinical settings.

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卡马西平的药物遗传学：关于 CYP3A4 和 CYP3A5 多态性的系统综述。

背景和目的：卡马西平（CBZ）在癫痫中的代谢和耐药性与 CYP3A5（rs776746 和 rs15524）和 CYP3A4（rs2242480、rs2740574、rs35599367、rs12721627 和 rs28371759）的基因多态性之间的关系一直是以往研究的主题，但结果存在争议。我们进行了一项系统综述，以评估这些多态性与 CBZ 代谢和耐药性之间的潜在联系：方法：通过搜索 PubMed、Scopus、PharmGKB、EPIGAD 和 PHARMAADME 数据库（截至 2023 年 6 月），确定相关研究。纳入分析的研究调查了 CYP3A5（rs776746 和 rs15524）和 CYP3A4（rs2242480、rs2740574、rs35599367、rs12721627 和 rs28371759）多态性与 CBZ 代谢和耐药性之间的联系：本综述共纳入 23 项研究和超过 2177 名癫痫患者。结果发现，CYP3A4（rs12721627 和 rs28371759）多态性与催化活性降低有关，而 CYP3A4（rs2740574）多态性与 CBZ-二醇水平降低和活性下降有关。研究还发现，CYP3A5（rs776746）多态性会影响CBZ的剂量调整血浆水平：尽管这些发现强调了 CYP3A4 和 CYP3A5 基因的遗传变异对 CBZ 药代动力学和药效学的影响，但要在临床环境中加强个性化癫痫治疗，必须在不同人群中开展进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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CNS & neurological disorders drug targets

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