• Kazuyuki Inoue, Eri Suzuki, Rei Yazawa, Yoshiaki Yamamoto, Toshiki Takahashi, Yukitoshi Takahashi, Katsumi Imai, Seiichi Koyama, Yushi Inoue, Daiki Tsuji, Hideki Hayashi, and Kunihiko Itoh.
• *Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka; and †Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, National Epilepsy Center, Shizuoka, Japan.
• Ther Drug Monit. 2014 Jun 1; 36 (3): 406-9.

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

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