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Pharmacogenetics of the antiepileptic drugs phenytoin and lamotrigine.

Drug metabolism and drug interactions (2011-05-12)
Marisol López, Pedro Dorado, Nancy Monroy, María Elisa Alonso, Helgi Jung-Cook, Esther Machín, Eva Peñas-Lledó, Adrián Llerena
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lamotrigine, ≥98%, powder
Supelco
Phenytoin, Pharmaceutical Secondary Standard; Certified Reference Material
Lamotrigine for system suitability, European Pharmacopoeia (EP) Reference Standard
USP
Lamotrigine, United States Pharmacopeia (USP) Reference Standard
Lamotrigine for peak identification, European Pharmacopoeia (EP) Reference Standard
Lamotrigine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
5,5-Diphenylhydantoin, ≥98%
Supelco
Lamotrigine, Pharmaceutical Secondary Standard; Certified Reference Material
Phenytoin, European Pharmacopoeia (EP) Reference Standard
USP
Phenytoin, United States Pharmacopeia (USP) Reference Standard
Supelco
Phenytoin solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Phenytoin for system suitability, European Pharmacopoeia (EP) Reference Standard
Supelco
Lamotrigine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®