title: Fatal hydrocodone overdose in a child: pharmacogenetics and drug interactions.
abstract: Fatal opioid toxicity occurred in a developmentally delayed child aged 5 years 9 months who was inadvertently administered high doses of hydrocodone for a respiratory tract infection. The concentration of hydrocodone in postmortem blood was in the range associated with fatality; however, hydromorphone, a major metabolite catalyzed by cytochrome P450 2D6 (CYP2D6), was not detected when using mass spectrometry. Genetic analysis revealed that the child had a reduced capability to metabolize the drug via the CYP2D6 pathway (CYP2D6*2A/*41). Coadministration of clarithromycin (a potent cytochrome P450 3A4 inhibitor) for an ear infection and valproic acid for seizures since birth further prevented drug elimination from the body. This case highlights the interplay between pharmacogenetic factors, drug-drug interactions, and dose-related toxicity in a child.
authors.affiliation: Motherisk Program, Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada M5G 1X8.
authors.forename: Parvaz
authors.initials: P
authors.lastname: Madadi
authors.forename: Doris
authors.initials: D
authors.lastname: Hildebrandt
authors.forename: Inna Y
authors.initials: IY
authors.lastname: Gong
authors.forename: Ute I
authors.initials: UI
authors.lastname: Schwarz
authors.forename: Catherine
authors.initials: C
authors.lastname: Ciszkowski
authors.forename: Colin J D
authors.initials: CJ
authors.lastname: Ross
authors.forename: Johanna
authors.initials: J
authors.lastname: Sistonen
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Carleton
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Albert E
authors.initials: AE
authors.lastname: Lauwers
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D000996:Antitussive Agents / Q000493:pharmacokinetics / Q000506:poisoning* / Q000627:therapeutic use; D002675:Child, Preschool; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D004347:Drug Interactions; D062787:Drug Overdose; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000493:pharmacokinetics / Q000506:poisoning* / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000996:Antitussive Agents; D014635:Valproic Acid; D006853:Hydrocodone; D019389:Cytochrome P-450 CYP2D6