Helixtalk - Rosalind Franklin University's College Of Pharmacy Podcast

167 - Beyond One-Size-Fits-All: Unraveling the Genetic Tapestry of CYP2D6 Drug Metabolism

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Synopsis

In this episode, we review the science behind genetic differences in humans in the CYP2D6 hepatic enzyme responsible for drug metabolism and how these genetic variants can lead to certain drugs being metabolized far too much or far too little, which can cause drug toxicities or a lack of effectiveness. Key Concepts About 20-25% of drugs on the market are metabolized by CYP2D6. Humans have a huge degree of variability in CYP2D6 metabolism ranging from “ultra” metabolizers to “poor” metabolizers. Drugs that heavily rely on CYP2D6 metabolism are prone to large variability in responses due to these genetic differences. Some drugs rely on metabolic inactivation of CYP2D6 whereas other drugs use the enzyme to become converted to a more active compound. Codeine and tramadol both heavily rely on CYP2D6 activation to a more potent opioid compound. Patients with excessive CYP2D6 activity will have toxicities (from too much of an active metabolite) whereas patients with low CYP2D6 activity will have little therapeutic