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A correction has been published: N Engl J Med 2005;352(6):638.

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Volume 351:2827-2831 December 30, 2004 Number 27
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Codeine Intoxication Associated with Ultrarapid CYP2D6 Metabolism
Yvan Gasche, M.D., Youssef Daali, Pharm.D., Ph.D., Marc Fathi, Ph.D., Alberto Chiappe, Silvia Cottini, M.D., Pierre Dayer, M.D., and Jules Desmeules, M.D.

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SUMMARY

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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From the Divisions of Surgical (Y.G., S.C.) and Medical Intensive Care (Y.G.), Clinical Pharmacology and Toxicology (Y.D., P.D., J.D.), and Clinical Chemistry (M.F., A.C.), Geneva University Hospital, Geneva.

Address reprint requests to Dr. Gasche at the Division of Surgical Intensive Care, Department of Anesthesiology, Pharmacology, and Surgical Intensive Care, Geneva University Hospital, 24 rue Micheli-du-Crest, CH-1211 Geneva, Switzerland, or at yvan.gasche{at}medecine.unige.ch.

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