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Ther Drug Monit. 2014 Jun;36(3):406-9. doi: 10.1097/FTD.0000000000000012.

Influence of uridine diphosphate glucuronosyltransferase 2B7 -161C>T polymorphism on the concentration of valproic acid in pediatric epilepsy patients.

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  • 1*Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka; and ‚ĆDepartment of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, National Epilepsy Center, Shizuoka, Japan.

Abstract

BACKGROUND:

Valproic acid (VPA) is widely used to treat various types of epilepsy. Interindividual variability in VPA pharmacokinetics may arise from genetic polymorphisms of VPA-metabolizing enzymes. This study aimed to examine the relationships between plasma VPA concentrations and the -161C>T single nucleotide polymorphism in uridine diphosphate glucuronosyltransferase (UGT) 2B7 genes in pediatric epilepsy patients.

METHODS:

This study included 78 pediatric epilepsy patients carrying the cytochrome P450 (CYP) 2C9*1/*1 genotype and who were not treated with the enzyme inducers (phenytoin, phenobarbital, and carbamazepine), lamotrigine, and/or topiramate. CYP2C9*3 and UGT2B7 -161C>T polymorphisms were identified using methods based on polymerase chain reaction-restriction fragment length polymorphism. Blood samples were drawn from each patient under steady-state conditions, and plasma VPA concentrations were measured.

RESULTS:

Significant differences in adjusted plasma VPA concentrations were observed between carriers of CC, CT, and TT genotypes in the UGT2B7 -161C>T polymorphism (P = 0.039). Patients with the CC genotype had lower adjusted plasma VPA concentrations than those with CT or TT genotype (P = 0.028).

CONCLUSIONS:

These data suggest that the UGT2B7 -161C>T polymorphism in pediatric epilepsy patients carrying the CYP2C9*1/*1 genotype affects VPA concentration.

PMID:
24365988
[PubMed - indexed for MEDLINE]
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