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

Margaret T. Susce, Elaina Murray-Carmichael, Jose de Leon

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Codeine is metabolized by the cytochrome P450 2D6 (CYP2D6) to morphine. Codeine is a much weaker agonist at μ opioid receptors than morphine. Therefore, codeine analgesia is highly dependent on CYP2D6 activity. Large prospective studies in the clinical environment do not exist, but it appears reasonable to avoid codeine use in CYP2D6 poor metabolizers (PMs). CYP2D6 metabolizes other opioid analgesics, including tramadol, dihydrocodeine, oxycodone and hydrocodone, although they have been less systematically studied. It is unclear whether these other pro-drugs may be as completely dependent on CYP2D6 for their analgesia as codeine. We describe a patient identified as a CYP2D6 PM with a history of problems with opioid analgesics. The patient was an 85-year-old female Caucasian who had hip surgery. The patient had a long-standing intolerance to codeine. In her first admission, she couldn't tolerate the regimen of oxycodone combined with tramadol prns (as needed). She was genotyped as a CYP2D6 PM and after the information was provided to the treating physician in her second admission, she seemed to have a better response to hydrocodone. Large case-control naturalistic studies followed by randomized trials in patients taking opioid analgesics may be needed to definitively establish that CYP2D6 genotyping has clinical relevance in the use of several opioid analgesics.

Original languageEnglish
Pages (from-to)1356-1358
Number of pages3
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Issue number7
StatePublished - Sep 30 2006

Bibliographical note

Funding Information:
This patient was genotyped with no external support. Roche Molecular Systems, Inc. markets the FDA-approved AmpliChip CYP450 microarray detecting the CYP2D6 and CYP2C19 gene variations using a technology developed by Affymetrix. Jose de Leon, M.D., has lectured once supported by Roche-Molecular Systems, Inc. He has also received support for his laboratory and research-initiated grants from Roche-Molecular Systems, Inc., but he has not received any consultant payments. He has no other financial arrangements with Roche Molecular Systems, Inc. He has no stocks from Roche or Affymetrix.


  • Analgesia
  • Codeine
  • Cytochrome P450 2D6
  • Genotyping
  • Hydrocodone
  • Oxycodone
  • Pain

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry


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