title: Pharmacogenetics of the antiepileptic drugs phenytoin and lamotrigine.
abstract: Patients treated with antiepileptic drugs can exhibit large interindividual variability in clinical efficacy or adverse effects. This could be partially due to genetic variants in genes coding for proteins that function as drug metabolizing enzymes, drug transporters or drug targets. The purpose of this article is to provide an overview of the current knowledge on the pharmacogenetics of two commonly prescribed antiepileptic drugs with similar mechanisms of action; phenytoin (PHT) and lamotrigine (LTG). These two drugs have been selected in order to model the pharmacogenetics of Phase I and Phase II metabolism for PHT and LTG, respectively. In light of the present evidence, patients treated with PHT could benefit from CYP2C9 and CYP2C19 genotyping/phenotyping. For those under treatment with LTG, UGT1A4 and UGT2B7 genotyping might be of clinical use and could contribute to the interindividual variability in LTG concentration to dose ratio in epileptic patients.
authors.affiliation: Department of Biological Systems, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico.
authors.forename: Marisol
authors.initials: M
authors.lastname: López
authors.forename: Pedro
authors.initials: P
authors.lastname: Dorado
authors.forename: Nancy
authors.initials: N
authors.lastname: Monroy
authors.forename: María Elisa
authors.initials: ME
authors.lastname: Alonso
authors.forename: Helgi
authors.initials: H
authors.lastname: Jung-Cook
authors.forename: Esther
authors.initials: E
authors.lastname: Machín
authors.forename: Eva
authors.initials: E
authors.lastname: Peñas-Lledó
authors.forename: Adrián
authors.initials: A
authors.lastname: Llerena
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D004827:Epilepsy / Q000188:drug therapy; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000077213:Lamotrigine; D010597:Pharmacogenetics; D010672:Phenytoin / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D014227:Triazines / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D010672:Phenytoin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D014453:Glucuronosyltransferase; D000077213:Lamotrigine