Codeine intoxication associated with ultrarapid CYP2D6 metabolism

N Engl J Med. 2004 Dec 30;351(27):2827-31. doi: 10.1056/NEJMoa041888.

Abstract

Life-threatening opioid intoxication developed in a patient after he was given small doses of codeine for the treatment of a cough associated with bilateral pneumonia. Codeine is bioactivated by CYP2D6 into morphine, which then undergoes further glucuronidation. CYP2D6 genotyping showed that the patient had three or more functional alleles, a finding consistent with ultrarapid metabolism of codeine. We attribute the toxicity to this genotype, in combination with inhibition of CYP3A4 activity by other medications and a transient reduction in renal function.

Publication types

  • Case Reports

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / metabolism*
  • Analgesics, Opioid / poisoning
  • Antitussive Agents / administration & dosage
  • Antitussive Agents / metabolism
  • Antitussive Agents / poisoning*
  • Codeine / administration & dosage
  • Codeine / metabolism
  • Codeine / poisoning*
  • Cough / drug therapy
  • Cough / etiology
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Dextromethorphan / metabolism
  • Dextromethorphan / therapeutic use
  • Genotype
  • Humans
  • Lung Diseases, Fungal / drug therapy
  • Male
  • Methylation
  • Middle Aged
  • Phenotype
  • Pneumonia / complications
  • Pneumonia / drug therapy

Substances

  • Analgesics, Opioid
  • Antitussive Agents
  • Dextromethorphan
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Codeine