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Publication Date:
May 2011
ISSN:
2191-0162
DOI:
10.1515/dmdi.2011.008

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Editor-in-Chief: Siest, Gérard

Editorial Board Member: Chen, Bing / Devinsky, Ferdinand / Henney, Adriano / Hirata, Rosario D. C. / Ingelman-Sundberg, Magnus / Llerena, Adrián / Manolopoulos, Vangelis G. / Meyer, Urs A. / Patrinos, George / Schaik, Ron / Sadee, Wolfgang / Turpeinen, Miia / Maitland-van de Zee, Anke-Hilse / Zanger, Ulrich M. / Marc, Janja / Hubacek, Jaroslav A.

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Pharmacogenetics of the antiepileptic drugs phenytoin and lamotrigine

Marisol López1, a / Pedro Dorado2, a / Nancy Monroy3 / María Elisa Alonso3 / Helgi Jung-Cook4, 5 / Esther Machín2 / Eva Peñas-Lledó2 / 2

1Department of Biological Systems, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico

2CICAB Clinical Research Center, Extremadura University Hospital and Medical School, Servicio Extremeño de Salud, Badajoz, Spain

3Department of Neurogenetics and Molecular Biology, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico

4Department of Neuropharmacology, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico

5Department of Pharmacy, Chemistry Faculty, Universidad Nacional Autónoma de México, Mexico City, Mexico

aM. López and P. Dorado contributed equally to this work.

Corresponding authors: Pedro Dorado/Adrián Llerena, CICAB Clinical Research Centre, Extremadura University Hospital and Medical School, Servicio Extremeño de Salud, Badajoz, Spain

Citation Information: Drug Metabolism and Drug Interactions. Volume 26, Issue 1, Pages 5–12, ISSN (Online) 2191-0162, ISSN (Print) 0792-5077, DOI: 10.1515/dmdi.2011.008, May 2011

Publication History:
Received:
2011-02-24
Accepted:
2011-04-05
Published Online:
2011-05-11

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.

Keywords: antiepileptic drug; cytochrome P450; lamotrigine; pharmacogenetics; phenytoin; UDP-glucuronosyltransferase (UGT)

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