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. 2001 Jul;52(1):100-3.
doi: 10.1046/j.0306-5251.2001.01411.x.

Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes

C Senda  1 , Y Yamaura, K Kobayashi, H Fujii, H Minami, Y Sasaki, T Igarashi, K Chiba
Affiliations

Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes

C Senda et al. Br J Clin Pharmacol. 2001 Jul.

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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Figures

Figure 1
Figure 1
Mexiletine hydroxylation activity in microsomes from human livers genotyped as CYP2D6*1/*1 (n = 5), *1/*10 (n = 6), *10/*10 (n = 6) and *5/*5 (n = 1). (a) PHM formation and (b) HMM formation. Each bar represents the mean value and the error bar represents s.d.
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