title: Codeine intoxication associated with ultrarapid CYP2D6 metabolism.
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.
authors.affiliation: Divisions of Surgical and Medical Intensive Care, Geneva University Hospital, Switzerland. yvan.gasche@medecine.unige.ch
authors.forename: Yvan
authors.initials: Y
authors.lastname: Gasche
authors.forename: Youssef
authors.initials: Y
authors.lastname: Daali
authors.forename: Marc
authors.initials: M
authors.lastname: Fathi
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiappe
authors.forename: Silvia
authors.initials: S
authors.lastname: Cottini
authors.forename: Pierre
authors.initials: P
authors.lastname: Dayer
authors.forename: Jules
authors.initials: J
authors.lastname: Desmeules
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000378:metabolism* / Q000506:poisoning; D000996:Antitussive Agents / Q000008:administration & dosage / Q000378:metabolism / Q000506:poisoning*; D003061:Codeine / Q000008:administration & dosage / Q000378:metabolism / Q000506:poisoning*; D003371:Cough / Q000188:drug therapy / Q000209:etiology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003915:Dextromethorphan / Q000378:metabolism / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008172:Lung Diseases, Fungal / Q000188:drug therapy; D008297:Male; D008745:Methylation; D008875:Middle Aged; D010641:Phenotype; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy
chemical_list: D000701:Analgesics, Opioid; D000996:Antitussive Agents; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D003061:Codeine