Citation

Madadi P, Hildebrandt D, Gong IY, Schwarz UI, Ciszkowski C, Ross CJD, Sistonen J, Carleton BC, Hayden MR, Lauwers AE, Koren G. Pediatrics 2010; 126(4): e986-9.

Affiliation

Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada;

Copyright

(Copyright © 2010, American Academy of Pediatrics)

DOI

10.1542/peds.2009-1907

PMID

20837591

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.

Language: en