title: Genetic polymorphisms associated with antiepileptic metabolism.
abstract: Several factors, including pharmacogenetics, contribute to inter-individual variability in drug response. Many antiepileptic drugs (AEDs) are metabolized by a variety of enzymatic reactions, and the cytochrome P450 (CYP) family has attracted considerable attention. Some of the CYPs exist as genetic (allelic) variants, which may also affect the plasma concentrations or drug exposure. Regarding the metabolism of AEDs, the polymorphic CYP2C9 and CYP2C19 are of particular interest. There have been recent advances in discovering factors such as these, especially those underlying the risk of medication toxicity. This review summarizes the evidence about whether such polymorphisms affect the clinical action of AEDs to facilitate future studies on the pharmacogenetics of epilepsy. We performed Key Words searches in the public databases PubMed, Medscape, and Rxlisty, Pharm GKB for genetic polymorphisms and the NCBI website for the nomenclature of alleles of CYP450, finding that CYP2D6, CYP2C9, CYP3A4, and CYP2D19 were involved in the metabolism of most antiepileptic drugs, given the allele frequency in the population and the associated variability in the clinical response.
authors.affiliation: Doctoral Biological and Health Sciences, Metropolitan Autonomous University, Mexico City, Mexico.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lopez-Garcia
authors.affiliation: Doctoral Biological and Health Sciences, Metropolitan Autonomous University, Mexico City, Mexico.
authors.forename: Iris A
authors.initials: IA
authors.lastname: Feria-Romero
authors.affiliation: Doctoral Biological and Health Sciences, Metropolitan Autonomous University, Mexico City, Mexico.
authors.forename: Hector
authors.initials: H
authors.lastname: Fernando-Serrano
authors.affiliation: Doctoral Biological and Health Sciences, Metropolitan Autonomous University, Mexico City, Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Escalante-Santiago
authors.affiliation: Doctoral Biological and Health Sciences, Metropolitan Autonomous University, Mexico City, Mexico.
authors.forename: Israel
authors.initials: I
authors.lastname: Grijalva
authors.affiliation: Doctoral Biological and Health Sciences, Metropolitan Autonomous University, Mexico City, Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Orozco-Suarez
mesh_terms: D000927:Anticonvulsants / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D005787:Gene Frequency; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D039781:PubMed
chemical_list: D000927:Anticonvulsants; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19