1. CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice
- Author
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C. Michael Stein, Cecilia P. Chung, Daniel A Carranza-Leon, Alyson L Dickson, and Andrea Gaedigk
- Subjects
Male ,0301 basic medicine ,Analgesic effect ,medicine.medical_specialty ,CYP2D6 ,Genotype ,030226 pharmacology & pharmacy ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Genetics ,Humans ,Medicine ,In patient ,Aged ,Pharmacology ,Response rate (survey) ,Polymorphism, Genetic ,Morphine ,Codeine ,business.industry ,Middle Aged ,Analgesics, Opioid ,Clinical Practice ,Phenotype ,030104 developmental biology ,Cytochrome P-450 CYP2D6 ,Molecular Medicine ,Female ,business ,medicine.drug - 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).
- Published
- 2021