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Towards personalized opioid dosing: A concise overview of CYP polymorphisms

Joseph V Pergolizzi Jr, Robert Taylor Jr, Jo Ann LeQuang, Robert B Raffa, Frank Breve

Concern about excess opioid prescribing and abuse makes it is more important than ever that the dose of opioid prescribed be sufficient to relieve pain, but not excessive. The wide variation among patients regarding opioid response poses clinical challenges to prescribers seeking to offer patients adequate but safe levels of analgesia. While many factors (pharmacodynamics and pharmacokinetic) can influence drug response, growing understanding of the genomic influences on the cytochrome (CYP) P450 enzymes may help better identify patients who will most benefit from opioid therapy and direct their dosing regimen. Since many opioids are primarily metabolized by Phase 1 CYP450 enzymes, CYP enzyme polymorphisms can result in variations in patient response. Many opioids and other drug classes are metabolized by the CYP families CYP2D6, CYP3A4, and to lesser extent CYP2B6 enzymes. Thus, patients who have genotype polymorphisms in these enzymes are phenotypically (clinically) poor, intermediate, extensive, or ultra-rapid metabolizers, affecting how rapidly or to what extent an individual patient metabolizes opioids. Moreover, these enzymes may be induced or inhibited by drugs or other substances. While phenotyping and genotyping individual patients is not yet a practical everyday solution, the advent of personalized medicine will likely allow for cost-effective, rapid testing that may better identify a patient’s metabolic type prior to prescribing opioid therapy. With better matching of the effective dose for each patient, it should be possible to avoid excess dosing, resulting in fewer prescribed pills and, presumably, fewer unused pills that are at risk for diversion.