Steven Yale, MD
Codeine is a drug that has been used for years to treat mild and moderate pain. One of the ways that it is metabolized results in the formation of morphine, which is believed to be the metabolite that makes codeine effective as a pain reliever.
The vast majority of clinically useful drugs are degraded by a small number of metabolic pathways, mainly microsomal P-450 enzymes located in the liver, and to a lesser extent, in the small intestine. A form of P-450 enzyme referred to as CYP2D6 metabolizes about 20% of the clinical drugs. Extensive studies on the CYP2D6 gene over the last decade have identified at least 53 alleles, and of these, more than 20 are known to significantly alter the metabolism of CYP2D6 substrates. CYP2D6 activity ranges from complete absence to ultra-rapid metabolism.
The ability of CYP2D6 to metabolize codeine to morphine is absent in 7% of the white population. This means that millions of patients get less pain relief from codeine because their particular variant of the CYP2D6 gene is unable to convert codeine into morphine.
In this study, it is planned to investigate a subpopulation of the Marshfield Clinic patients that have a medical history of relative codeine insensitivity to identify their genetic polymorphisms and to stratify this subpopulation into groups exhibiting pharmacokinetic differences in codeine metabolism.