The clinical impact of cytochrome P450 polymorphisms on anti-epileptic drug therapy

Abstract

The goal of pharmacogenetics is to deliver safe and effective drug therapy. Genetic polymorphisms in cytochrome P450 (CYP) enzyme genes are implicated in the inter-individual variability in pharmacokinetics of antiepileptic drugs (AEDs). However, the clinical impact of CYP polymorphisms on AED therapy remains controversial. Previous studies have shown that the defective CYP2C9 alleles affect the required dose of phenytoin and the risk of its toxicity. We have reported that the CYP2C19-deficient genotype is associated with the serum concentration of an active metabolite of clobazam, N-desmethylclobazam, and with the clinical efficacy of clobazam therapy. We determined also the influence of polymorphisms in CYP genes on the population pharmacokinetic parameters of AEDs us-