Aims To study the influence of CYP2D6*10 on the formation of p-hydroxymexil
etine (PHM) and hydroxymethylmexiletine (HMM) using microsomes from human l
iver of known genotypes.
Methods Microsomes from human livers of genotype CYP2D6*1/*1 (n = 5), *1/*1
0 (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.
Concl(u)sions The metabolism of mexiletine to form PHM and HMM appears to b
e impaired to a significant extent in human liver microsomes from hetero- a
nd homozygotes of CYP2D6*10.