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

Codeine intoxication associated with ultrarapid CYP2D6 metabolism.

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Divisions of Surgical and Medical Intensive Care, Geneva University Hospital, Switzerland.

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  • N Engl J Med. 2005 Feb 10;352(6):638.


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.

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