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Codeine intoxication associated with ultrarapid CYP2D6 metabolism

Chiappe, Alberto
Published in New England Journal of Medicine. 2004, vol. 351, no. 27, p. 2827-2831
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.
Keywords Analgesics, Opioid/administration & dosage/metabolism/poisoningAntitussive Agents/administration & dosage/metabolism/poisoningCodeine/administration & dosage/metabolism/poisoningCough/drug therapy/etiologyCytochrome P-450 CYP2D6/genetics/metabolismCytochrome P-450 CYP3ACytochrome P-450 Enzyme System/genetics/metabolismDextromethorphan/metabolism/therapeutic useGenotypeHumansLung Diseases, Fungal/drug therapyMaleMethylationMiddle AgedPhenotypePneumonia/complications/drug therapy
PMID: 15625333
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Research groups Pharmaco-omiques et médecine de précision (1003)
Groupe Desmeules Jules (pharmacologie/toxicologie) (567)
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GASCHE, Yvan et al. Codeine intoxication associated with ultrarapid CYP2D6 metabolism. In: New England Journal of Medicine, 2004, vol. 351, n° 27, p. 2827-2831. doi: 10.1056/NEJMoa041888 https://archive-ouverte.unige.ch/unige:90087

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Deposited on : 2016-12-08

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