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Codeine metabolizer status in clinical practice

Apr. 5, 2021, 8:00 AM

by Leigh MacMillan

Codeine — widely prescribed for pain — is inactive until it is metabolized to morphine by the enzyme CYP2D6. CYP2D6 activity is affected by genetic variation with “poor metabolizers” (PMs) producing almost no morphine from codeine and “intermediate metabolizers” (IMs) having reduced benefit. 

Most patients receive codeine without CYP2D6 genotyping, and the utility of testing for metabolizer status in clinical practice is poorly defined. 

Cecilia Chung, MD, MPH, and colleagues used BioVU, Vanderbilt’s DNA biobank linked to de-identified electronic health records, to study 157 patients who received codeine. They found that patients in the PM or IM groups (44%) had lower rates of pain response while receiving codeine compared to the normal and ultrarapid metabolizer groups. 

The researchers developed a response score that includes CYP2D6 phenotype and clinical variables. Their findings, reported in The Pharmacogenomics Journal, support using genetic and clinical information to prescribe an alternate analgesic to patients with a codeine response score resulting in pain response rate below 10%.

This research was supported by the National Institutes of Health (grants GM109145, GM131770, AR073764) and the Veterans Health Administration.

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