title: Influence of uridine diphosphate glucuronosyltransferase 2B7 -161C>T polymorphism on the concentration of valproic acid in pediatric epilepsy patients.
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.
authors.affiliation: *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.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.forename: Eri
authors.initials: E
authors.lastname: Suzuki
authors.forename: Rei
authors.initials: R
authors.lastname: Yazawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Toshiki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
authors.forename: Seiichi
authors.initials: S
authors.lastname: Koyama
authors.forename: Yushi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Daiki
authors.initials: D
authors.lastname: Tsuji
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000367:Age Factors; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D014635:Valproic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D065729:Cytochrome P-450 CYP2C9; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase