Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy.
Int J Mol Sci. 2023 Jan 28;24(3):2535. doi: 10.3390/ijms24032535.
Epilepsy is one of the most frequent chronic neurologic disorders that affects nearly 1% of the population worldwide, especially in developing countries. Currently, several antiepileptic drugs (AEDs) are available for its therapy, and although the prognosis is good for most patients, 20%-30% amongst them do not reach seizure freedom. Numerous factors may explain AED-resistance such as sex, age, ethnicity, type of seizure, early epilepsy onset, suboptimal dosing, poor drug compliance, alcohol abuse, and in particular, genetic factors. Specifically, the interindividual differences in drug response can be caused by single nucleotide polymorphisms (SNPs) in genes encoding for drug efflux transporters, for the brain targets of AEDs, and for enzymes involved in drug metabolism. In this review, we used the PubMed database to retrieve studies that assessed the influence of SNPs on the pharmacokinetic (PK), pharmacodynamic (PD), and efficacy of new antiepileptic drugs. Our results showed that polymorphisms in the ABCB1, ABCC2, UGT1A4, UGT2B7, UGT2B15, CYP2C9, and CYP2C19 genes have an influence on the PK and efficacy of AEDs, suggesting that a genetic pre-evaluation of epileptic patients could help clinicians in prescribing a personalized treatment to improve the efficacy and the safety of the therapy.
癫痫是最常见的慢性神经系统疾病之一,影响着全球近 1%的人口,尤其在发展中国家。目前,有多种抗癫痫药物(AEDs)可用于治疗癫痫,尽管大多数患者的预后良好,但仍有 20%-30%的患者无法达到无发作状态。许多因素可能导致 AED 耐药,如性别、年龄、种族、发作类型、癫痫早期发作、剂量不足、药物依从性差、酒精滥用,特别是遗传因素。具体来说,药物反应的个体间差异可能是由于编码药物外排转运体、AED 脑靶点和参与药物代谢的酶的基因中的单核苷酸多态性(SNPs)引起的。在这篇综述中,我们使用 PubMed 数据库检索了评估 SNPs 对新型抗癫痫药物的药代动力学(PK)、药效学(PD)和疗效影响的研究。我们的结果表明,ABCB1、ABCC2、UGT1A4、UGT2B7、UGT2B15、CYP2C9 和 CYP2C19 基因的多态性对 AEDs 的 PK 和疗效有影响,这表明对癫痫患者进行遗传预评估可以帮助临床医生制定个性化治疗方案,以提高治疗的疗效和安全性。