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Related Experiment Videos

Response to hydrocodone, codeine and oxycodone in a CYP2D6 poor metabolizer.

Margaret T Susce1, Elaina Murray-Carmichael, Jose de Leon

  • 1University of Kentucky, Mental Health Research Center at Eastern State Hospital, Lexington, KY 40508, USA.

Progress in Neuro-Psychopharmacology & Biological Psychiatry
|April 25, 2006
PubMed
Summary

Codeine analgesia depends on CYP2D6 enzyme activity. Patients who are CYP2D6 poor metabolizers (PMs) may not effectively process codeine, suggesting caution with its use in this population.

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Area of Science:

  • Pharmacogenomics
  • Clinical Pharmacology
  • Drug Metabolism

Background:

  • Codeine is a prodrug requiring metabolism by cytochrome P450 2D6 (CYP2D6) into morphine for analgesia.
  • CYP2D6 activity significantly influences the efficacy of codeine, a weaker opioid agonist than its metabolite, morphine.
  • CYP2D6 also metabolizes other opioid analgesics, including tramadol, oxycodone, and hydrocodone, but their dependence on this enzyme is less understood.

Observation:

  • A case study involving an 85-year-old female CYP2D6 poor metabolizer (PM) with a history of opioid analgesic intolerance is presented.
  • The patient experienced adverse effects with oxycodone and tramadol, but showed improved response to hydrocodone after CYP2D6 genotyping results were considered.
  • This case highlights potential challenges in pain management for individuals with specific genetic variations in drug-metabolizing enzymes.

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Findings:

  • Codeine's analgesic effect is directly linked to CYP2D6 enzymatic activity.
  • Individuals identified as CYP2D6 poor metabolizers (PMs) may not achieve adequate pain relief from codeine.
  • The clinical relevance of CYP2D6 genotyping for other opioid pro-drugs warrants further investigation.

Implications:

  • Avoiding codeine in CYP2D6 poor metabolizers (PMs) is a reasonable clinical consideration.
  • Further research, including large-scale studies and randomized trials, is necessary to confirm the clinical utility of CYP2D6 genotyping for various opioid analgesics.
  • Personalized pain management strategies may benefit from incorporating pharmacogenetic information to optimize opioid therapy.