title: Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes.
abstract: OBJECTIVE
  To study the influence of CYP2D6*10 on the formation of p-hydroxymexiletine (PHM) and hydroxymethylmexiletine (HMM) using microsomes from human liver of known genotypes.
  
  
  METHODS
  Microsomes from human livers of genotype CYP2D6*1/*1 (n = 5), *1/*10 (n = 6) and *10/*10 (n = 6) were used in this study. The formation of PHM and HMM was determined by high-performance liquid chromatography.
  
  
  RESULTS
  The formation rates of PHM and HMM were decreased by more than 50% and 85% in CYP2D6*1/*10 and *10/*10 microsomes, respectively, compared with *1/*1 microsomes.
  
  
  CONCLUSIONS
  The metabolism of mexiletine to form PHM and HMM appears to be impaired to a significant extent in human liver microsomes from hetero- and homozygotes of CYP2D6*10.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co, Hyogo.
authors.forename: C
authors.initials: C
authors.lastname: Senda
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaura
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.forename: H
authors.initials: H
authors.lastname: Minami
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Igarashi
authors.forename: K
authors.initials: K
authors.lastname: Chiba
mesh_terms: D000483:Alleles; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006900:Hydroxylation; D008801:Mexiletine / Q000493:pharmacokinetics*; D008862:Microsomes, Liver / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D019389:Cytochrome P-450 CYP2D6