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Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes

  1. T. Kubota1,2,
  2. Y. Yamaura2,
  3. N. Ohkawa1,
  4. H. Hara1,
  5. K. Chiba2

Article first published online: 24 DEC 2001

DOI: 10.1046/j.1365-2125.2000.00209.x

Issue

British Journal of Clinical Pharmacology

British Journal of Clinical Pharmacology

Volume 50, Issue 1, pages 31–34, July 2000

Additional Information

How to Cite

Kubota, T., Yamaura, Y., Ohkawa, N., Hara, H. and Chiba, K. (2000), Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes. British Journal of Clinical Pharmacology, 50: 31–34. doi: 10.1046/j.1365-2125.2000.00209.x

Author Information

  1. 1

    Research Testing Department, SRL Inc., Hachioji-shi, Tokyo and

  2. 2

    Faculty of Pharmaceutical Sciences, Chiba University, Chiba-Shi, Chiba, Japan

* Dr Kan Chiba, Faculty of Pharmaceutical Sciences, Chiba University, 1–33 Yayoi-cho, Inage-ku, Chiba-shi, Chiba 263–8522, Japan. Phone/Fax: 81 43 2902919; E-mail: kchiba@p.chiba-u.ac.jp

Publication History

  1. Issue published online: 24 DEC 2001
  2. Article first published online: 24 DEC 2001
  3. Received 11 November 1999, accepted 23 February 2000.

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Keywords:

  • CYP2D6*10;
  • CYP2D6*14;
  • dextromethorphan;
  • Japanese

Aims To determine the frequencies of 11 CYP2D6 mutant alleles (CYP2D6*2,*3,*4,*5,*8,*10,*11,*12,*14,*17 and *18), and their relation to the metabolic capacity of CYP2D6 in Japanese subjects.

Methods One hundred and sixty-two unrelated healthy Japanese subjects were genotyped with the polymerase chain reaction amplification method and 35 subjects were phenotyped with dextromethorphan.

Results The frequencies of CYP2D6*2,*5, *10 and *14 were 12.9, 6.2, 38.6 and 2.2% in our Japanese subjects, respectively. CYP2D6*3, *4, *8, *11, *12, *17 and *18 were not detected. The mean log metabolic ratio of dextromethorphan in subjects with genotypes predicting intermediate metabolizers was significantly greater than that of heterozygotes for functional and defective alleles.

ConclusionsCYP2D6*5 and CYP2D6*14 are the major defective alleles found in Japanese subjects. In addition, CYP2D6*10 may play a more important role than previously thought for the treatment of Japanese patients with drugs metabolized by CYP2D6.

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