Ecole Supérieure en Sciences Biologiques d'Oran (ESSBO), BP 1042, Saim Mohamed 31003, Oran, Algeria.
Laboratoire de Toxicologie, Environnement et santé, LATES, USTO-MB, Algeria.
CNS Neurol Disord Drug Targets. 2024;23(12):1463-1473. doi: 10.2174/0118715273298953240529100325.
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.
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.
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.
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.
卡马西平（CBZ）代谢与癫痫耐药之间的关联，以及 CYP3A5（rs776746 和 rs15524）和 CYP3A4（rs2242480、rs2740574、rs35599367、rs12721627 和 rs28371759）的遗传多态性一直是先前研究的主题，但结果存在争议。因此，我们进行了系统评价，以评估这些多态性与 CBZ 代谢和耐药之间的潜在联系。
通过检索 PubMed、Scopus、PharmGKB、EPIGAD 和 PHARMAADME 数据库，截至 2023 年 6 月，我们进行了相关研究的识别。我们分析中包含的研究调查了 CYP3A5（rs776746 和 rs15524）和 CYP3A4（rs2242480、rs2740574、rs35599367、rs12721627 和 rs28371759）多态性与 CBZ 代谢和耐药之间的联系。
本综述共纳入 23 项研究，涉及超过 2177 例癫痫患者。结果发现，CYP3A4（rs12721627 和 rs28371759）多态性与催化活性降低相关，而 CYP3A4（rs2740574）多态性与 CBZ-二醇水平降低和活性降低有关。还观察到 CYP3A5（rs776746）多态性影响 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，但在不同人群中进行进一步的研究对于增强临床环境中的个体化癫痫治疗至关重要。
