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

被引：19
|
作者：
Senda, C
Yamaura, Y
Kobayashi, K
Fujii, H
Minami, H
Sasaki, Y
Igarashi, T
Chiba, K
机构：
[1] Chiba Univ, Fac Pharmaceut Sci, Biochem Pharmacol & Biotoxicol Lab, Inage Ku, Chiba 2638522, Japan
[2] Natl Canc Ctr Hosp E, Chiba, Japan
[3] Nippon Boehringer Ingelheim Co, Kawanishi Pharma Res Inst, Dept Drug Metab & Pharmacokinet, Kawanishi, Hyogo, Japan
来源：
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY | 2001年 / 52卷 / 01期
关键词：
CYP2D6*10; human liver microsomes; mexiletine;
D O I：
10.1046/j.0306-5251.2001.01411.x
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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. Concl(u)sions 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.
引用
收藏
页码：100 / 103
页数：4
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