Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes |
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| Authors: | C Senda Y Yamaura K Kobayashi H Fujii H Minami Y Sasaki T Igarashi K Chiba |
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| Affiliation: | Department of Drug Metabolism and Pharmacokinetics, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co, Hyogo. |
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| Abstract: | AIMS: 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. |
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| Keywords: | CYP2D6*10 human liver microsomes mexiletine |
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