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CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice

The Pharmacogenomics Journal volume 21, pages 484–490 (2021)Cite this article

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Abstract

Cytochrome P450 2D6 (CYP2D6) O-demethylates codeine to the active drug, morphine. However, the utility of testing for CYP2D6 metabolizer status in patients receiving codeine in real-world clinical practice is poorly defined. Using data from a DNA bank linked to de-identified electronic health records, we studied 157 patients with a baseline pain score higher than 4 (0–10 scale) who received codeine. Based on CYP2D6 genotyping, 69 were classified as poor/intermediate and 88 as normal/ultrarapid CYP2D6 metabolizers. Pain response was defined as a score of 4 or lower while receiving codeine. In a propensity-score adjusted model, poor/intermediate metabolizers had lower odds (OR = 0.35, p = 0.02) of achieving a pain response than normal/ultrarapid metabolizers. To discriminate between codeine responders and nonresponders, a score including CYP2D6 phenotype and clinical variables was built. The response rate was 38.5% among patients in the high, 17.3% in the intermediate, and 9.4% in the low-score groups, respectively (p = 0.001).

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Acknowledgements

This study was supported by grants R01GM109145 and R35GM131770. CPC and ALD were also supported by grant R01AR073764 and the Veterans Health Administration Merit Award 1I01CX001741. The data set(s) used for the analyses described were obtained from Vanderbilt University Medical Center’s BioVU, which is supported by numerous sources: institutional funding, private agencies, and federal grants. These include the NIH funded Shared Instrumentation grant S10RR025141; and CTSA grants UL1TR002243, UL1TR000445, and UL1RR024975. Genomic data are also supported by investigator-led projects that include U01HG004798, R01NS032830, RC2GM092618, P50GM115305, U01HG006378, U19HL065962, R01HD074711; and additional funding sources are listed at https://victr.vumc.org/biovu/index.html?sid=229. The funding sources had no role in the collection, analysis, or interpretation of data, writing of the paper, or decision to submit for publication.

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Authors and Affiliations

  1. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Daniel Carranza-Leon, Alyson L. Dickson, C. Michael Stein & Cecilia P. Chung

  2. Division of Clinical Pharmacology Toxicology & Therapeutic Innovation, Children’s Mercy Kansas City, Kansas, MO, USA

    Andrea Gaedigk

  3. University of Missouri-Kansas City, School of Medicine, Kansas, MO, USA

    Andrea Gaedigk

  4. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA

    C. Michael Stein

  5. Tennessee Valley Healthcare System—Nashville Campus, Nashville, TN, USA

    Cecilia P. Chung

  6. Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA

    Cecilia P. Chung

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  1. Daniel Carranza-Leon
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Correspondence to Cecilia P. Chung.

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Carranza-Leon, D., Dickson, A.L., Gaedigk, A. et al. CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice. Pharmacogenomics J 21, 484–490 (2021). https://doi.org/10.1038/s41397-021-00226-8

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