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
相关论文
共 50 条
  • [41] Differentially altered metabolism and inhibition of CYP2D6*10.
    Ramamoorthy, Y
    Suh, N
    Tyndale, RF
    Sellers, EM
    CLINICAL PHARMACOLOGY & THERAPEUTICS, 2000, 67 (02) : 121 - 121
  • [42] Interactions of amphetamine analogs with human liver CYP2D6
    Wu, DF
    Otton, SV
    Inaba, T
    Kalow, W
    Sellers, EM
    BIOCHEMICAL PHARMACOLOGY, 1997, 53 (11) : 1605 - 1612
  • [43] Frequency of CYP2D6*10 and *14 alleles and their influence on the metabolic activity of CYP2D6 in a healthy Chinese population
    Cai, W. M.
    Chen, B.
    Zhang, W. X.
    CLINICAL PHARMACOLOGY & THERAPEUTICS, 2007, 81 (01) : 95 - 98
  • [44] Developmental changes in human liver CYP2D6 expression
    Stevens, Jeffrey C.
    Marsh, Sandra A.
    Zaya, Matthew J.
    Regina, Karen J.
    Divakaran, Karthika
    Le, Min
    Hines, Ronald N.
    DRUG METABOLISM AND DISPOSITION, 2008, 36 (08) : 1587 - 1593
  • [45] INTERINDIVIDUAL VARIABILITY IN CYP2D6 ACTIVITY IN HUMAN LIVER MICROSOMES TO CHARACTERIZE RARE GENETIC VARIATION.
    Dalton, R.
    Phillips, B.
    Risler, L.
    Shen, D. D.
    Woodahl, E. L.
    CLINICAL PHARMACOLOGY & THERAPEUTICS, 2015, 97 : S65 - S66
  • [46] GENOTYPE- SENSITIVE REVERSIBLE AND TIME-DEPENDENT CYP2D6 INHIBITION IN HUMAN LIVER MICROSOMES
    Storelli, Flavia
    Desmeules, Jules
    Daali, Youssef
    DRUG METABOLISM AND PHARMACOKINETICS, 2019, 34 (01) : S41 - S42
  • [47] Tri-Allelic Haplotypes Determine and Differentiate Functionally Normal Allele CYP2D6*2 and Impaired Allele CYP2D6*41
    Zanger, Ulrich M.
    Momoi, Kyoko
    Hofmann, Ute
    Schwab, Matthias
    Klein, Kathrin
    CLINICAL PHARMACOLOGY & THERAPEUTICS, 2021, 109 (05) : 1256 - 1264
  • [48] Effect of cimetidine on dextromethorphan O-demethylase activity of human liver microsomes and recombinant CYP2D6
    Bellward, GD
    Madeira, ML
    Levine, M
    Chang, TKH
    Mirfazaelian, A
    DRUG METABOLISM REVIEWS, 2004, 36 : 274 - 274
  • [49] Genotype-sensitive reversible and time-dependent CYP2D6 inhibition in human liver microsomes
    Storelli, Flavia
    Desmeules, Jules
    Daali, Youssef
    BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 2019, 124 (02) : 170 - 180
  • [50] Variable contribution of CYP2D6 to the N-dealkylation of S-(-)-propranolol by human liver microsomes
    Rowland, K
    Ellis, SW
    Lennard, MS
    Tucker, GT
    BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1996, 42 (03) : 390 - 393
12345