CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice
- 9 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in The Pharmacogenomics Journal
- Vol. 21 (4), 484-490
- https://doi.org/10.1038/s41397-021-00226-8
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).Keywords
Funding Information
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R01GM109145, R35GM131770)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
This publication has 19 references indexed in Scilit:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) GenotypeClinical Pharmacology & Therapeutics, 2011
- Pain in Patients with Cancer: The World Health Organization Analgesic Ladder and BeyondClinical Oncology, 2011
- Principles of Human Subjects Protections Applied in an Opt‐Out, De‐identified BiobankClinical and Translational Science, 2010
- New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzymeDrug Metabolism Reviews, 2009
- Development of a Large-Scale De-Identified DNA Biobank to Enable Personalized MedicineClinical Pharmacology & Therapeutics, 2008
- Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplicationThe Pharmacogenomics Journal, 2006
- The minimum clinically significant difference in visual analogue scale pain score does not differ with severity of painEmergency Medicine Journal, 2001
- PS power and sample size program available for free on the internetControlled Clinical Trials, 1997
- Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effectsEuropean Journal of Clinical Pharmacology, 1996
- Impact of environmental and genetic factors on codeine analgesiaEuropean Journal of Clinical Pharmacology, 1991