title: The influence of cytochrome oxidase CYP2A6, CYP2B6, and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients.
abstract: OBJECTIVE
  To investigate influences of the functional polymorphisms of Cytochrome P450 isozymes 2A6 (CYP2A6), 2B6 (CYP2B6), and 2C9 (CYP2C9) on pharmacokinetics of VPA in vivo.
  
  
  METHODS
  In the study, we analyzed the genotypes of CYP2A6, CYP2B6, and CYP2C9 and their contribution to the steady-state standardized plasma VPA concentrations in 179 subjects with epilepsy of a Northern Han Chinese population. The genotypes were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
  
  
  RESULTS
  The subjects with one or two variant CYP2A6*4 alleles showed higher mean plasma VPA concentrations compared with non-*4 alleles [(3.4+/-0.4)microg kg ml(-1)mg(-1) vs. (3.6+/-0.4)microg kg ml(-1)mg(-1), p=0.0055]. A significant difference [one-way ANOVA (p=0.0203)] was also found between mean plasma VPA concentrations and the CYP2B6 genotypes. In addition, subjects with the heterozygous genotype CYP2C9*3 had higher mean plasma VPA concentrations than did those subjects with the wild-type genotype [(3.9+/-0.4)microg kg ml(-1)mg(-1) vs. (3.4+/-0.4)microg kg ml(-1)mg(-1), p=0.0001].
  
  
  CONCLUSIONS
  The presently evaluated variant alleles in the CYP2A6, CYP2B6, and CYP2C9 genes may explain part of the substantial variability in VPA pharmacokinetics between different subjects.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071, China. dr.tanlan@163.com
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Sun
authors.forename: Jiang-Rong
authors.initials: JR
authors.lastname: Ou
authors.forename: Jing-Hui
authors.initials: JH
authors.lastname: Song
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; D065729:Cytochrome P-450 CYP2C9; D004827:Epilepsy / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D011110:Polymorphism, Genetic; D014635:Valproic Acid / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D014635:Valproic Acid; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; C585599:CYP2B6 protein, human; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating