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CYP2D6 Genotyping as an alternative to phenotyping for determination of metabolic status in a clinical trial setting

Content Provider	Springer Nature Link
Author	McElroy, Suzin Richmond, Jodi Lira, Maruja Friedman, David Silber, B. Michael Milos, Patrice M. Sachse, Christoph Brockmöller, Jürgen Roots, Ivar
Copyright Year	2000
Abstract	The emerging application of pharmacogenomics in the clinical trial setting requires careful comparison with more traditional phenotyping methodologies, particularly in the drug metabolism area where phenotyping is used extensively. The research objectives of this study were 1) to assess the utility of cytochrome P450 2D6 (CYP2D6) genotyping as an alternative to traditional phenotyping as a predictor of poor metabolizer status; 2) to identify issues for consideration when implementing CYP2D6 genotyping in clinical trials; and 3) to outline the advantages and disadvantages of CYP2D6 genotyping compared with phenotyping. DNA samples obtained from 558 previously phenotyped individuals were blindly genotyped at the CYP2D6 locus, and the genotype-phenotype correlation was then determined. The CYP2D6 genotyping methodology successfully predicted all but 1 of the 46 poor metabolizer subjects, and it was determined that this 1 individual had a novel (presumably inactive) mutation within the coding region. In addition, we identified 2 subjects with CYP2D6 genotypes indicative of poor metabolizers who had extensive metabolizer phenotypes as determined by dextromethorphan/dextrorphan ratios. This finding suggests that traditional phenotyping methods do not always offer 100% specificity. Our results suggest that CYP2D6 genotyping is a valid alternative to traditional phenotyping in a clinical trial setting, and in some cases may be better. We also discuss some of the issues and considerations related to the use of genotyping in clinical trials and medical practice.
Starting Page	1
Ending Page	11
Page Count	11
File Format	PDF
ISSN	12341234
Journal	The AAPS Journal
Volume Number	2
Issue Number	4
e-ISSN	15221059
Language	English
Publisher	Springer New York
Publisher Date	2000-10-29
Publisher Institution	American Association of Pharmaceutical Scientists
Publisher Place	New York
Access Restriction	Subscribed
Subject Keyword	Cytochrome P450 2D6 Pharmacogenomics Drug Metabolism Genotyping Pharmacology/Toxicology Biochemistry Biotechnology Pharmacy
Content Type	Text
Resource Type	Article

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