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

页码：100 / 103

页数：4

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