Impact of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms on antiepileptic drug safety and efficacy

A review of literature data is presented on polymorphic variants of genes responsible for antiepileptic drugs (AEDs) pharmacokinetics: highly polymorphic cytochrome P450 isoenzyme genes CYP2C9 and CYP2C19 as well as the gene ABCB1 encoding transporter protein P-glycoprotein. Genetic variants in CYP2C9 and CYP2C19 reduce the rate of metabolism, leading to AED ineffectiveness and adverse effects. ABCB1 gene polymorphisms affect the expression of P-glycoprotein in the intestine and the blood-brain barrier, preventing drug penetration into the brain and leading to drug resistance. AEDs pharmacogenetic studies are of high medical priority, as they contribute to creating scientific foundation for personalized epilepsy treatment, development of drug dosing recommendations, increasing efficacy and safety of commonly administered AEDs. Further studies in different patient groups are needed to improve individualized epilepsy treatment in clinical practice.