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Eur J Clin Pharmacol. 2010 Oct;66(10):1065-8. doi: 10.1007/s00228-010-0876-4. Epub 2010 Aug 11.

Limited effects of frequent CYP2D6*36-*10 tandem duplication allele on in vivo dextromethorphan metabolism in a Japanese population.

Author information

1
Laboratory for Pharmacogenetics, RIKEN Center for Medicine, Yokohama 230-0045, Japan.

Abstract

PURPOSE:

although CYP2D6*36 was thought to be one of the alleles causing the poor metabolizer phenotype, several in vitro studies clarified that the enzyme produced by CYP2D6*36 showed enzymatic activities. However, the effects of CYP2D6*36 in tandem with CYP2D6*10 on the in vivo CYP2D6 activity have been unclear. In this study, we investigated in vivo metabolic capacities of CYP2D6 among the subjects carrying different numbers of CYP2D6*36 in tandem with CYP2D6*10.

METHODS:

we measured the metabolic ratio (MR) of dextromethorphan in 98 subjects. We determined the CYP2D6 genotype of these subjects, including allelic copy number of CYP2D6*10 and CYP2D6*36 by direct sequencing, TaqMan assay, and real-time Invader assay.

RESULTS:

single copies of CYP2D6*10 and tandem duplication of CYP2D6*36-*10 alleles were found at frequencies of 8.7 and 32.7%, respectively. Median dextromethorphan MRs of the subjects carrying CYP2D6*10 and CYP2D6*36-*10 were not significantly different (Pā€‰=ā€‰0.24).

CONCLUSIONS:

CYP2D6*36 in tandem with CYP2D6*10 plays a minor role in interindividual variation of dextromethorphan metabolism in vivo.

PMID:
20700584
DOI:
10.1007/s00228-010-0876-4
[Indexed for MEDLINE]

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