CYP2D6*10等位基因对人肝微粒体代谢美西律的影响。
Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes.
作者信息
Senda C, Yamaura Y, Kobayashi K, Fujii H, Minami H, Sasaki Y, Igarashi T, Chiba K
机构信息
Department of Drug Metabolism and Pharmacokinetics, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co, Hyogo.
出版信息
Br J Clin Pharmacol. 2001 Jul;52(1):100-3. doi: 10.1046/j.0306-5251.2001.01411.x.
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.
目的
利用已知基因型的人肝脏微粒体研究CYP2D6*10对去甲羟利多卡因（PHM）和羟甲基利多卡因（HMM）形成的影响。
方法
本研究使用了基因型为CYP2D6*1/*1（n = 5）、*1/10（n = 6）和10/*10（n = 6）的人肝脏微粒体。通过高效液相色谱法测定PHM和HMM的形成。
结果
与CYP2D6*1/1微粒体相比，CYP2D61/10和10/*10微粒体中PHM和HMM的形成速率分别降低了50%以上和85%以上。
结论
在CYP2D6*10杂合子和纯合子的人肝脏微粒体中，美西律代谢形成PHM和HMM的过程似乎受到了显著损害。
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