Fatal and severe codeine intoxication in 3-year-old twins--interpretation of drug and metabolite concentrations

Int J Legal Med. 2009 Sep;123(5):387-94. doi: 10.1007/s00414-009-0340-0. Epub 2009 Apr 7.

Abstract

This work presents two cases of codeine intoxication in 3-year-old monozygotic twin brothers while treated with a codeine slow-release formulation. One child had to be admitted to the hospital, whereas the other one died at home after aspiration of gastric content. The concentrations of codeine and major metabolites including morphine and corresponding glucuronide conjugates were measured by liquid chromatography-tandem mass spectrometry in serum, urine, cerebrospinal fluid, and brain tissue, respectively. A genetic polymorphism study was carried out in order to determine the ability of the children to metabolize codeine by O-demethylation. A pharmacokinetic calculation was also performed to estimate the administered dose of codeine in question. High concentrations of all substances were found in samples of both children. The pharmacokinetic estimate suggests an overdose of codeine, and the possible reasons for the high opiate concentrations are discussed. Furthermore, the postmortem distribution--during and after resuscitation--might play a major role in the interpretation of postmortem concentration levels.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitussive Agents / analysis
  • Antitussive Agents / pharmacokinetics*
  • Antitussive Agents / poisoning*
  • Brain Chemistry
  • Brain Edema / pathology
  • Child, Preschool
  • Chromatography, Liquid
  • Codeine / analogs & derivatives
  • Codeine / analysis
  • Codeine / pharmacokinetics*
  • Codeine / poisoning*
  • Cytochrome P-450 CYP2D6 / genetics
  • Delayed-Action Preparations
  • Drug Overdose
  • Fatal Outcome
  • Forensic Toxicology
  • Genotype
  • Glucuronides / analysis
  • Humans
  • Medication Errors*
  • Morphine / analysis
  • Morphine Derivatives / analysis
  • Polymorphism, Genetic
  • Respiratory Aspiration / pathology
  • Tandem Mass Spectrometry
  • Tissue Distribution
  • Twins, Monozygotic

Substances

  • Antitussive Agents
  • Delayed-Action Preparations
  • Glucuronides
  • Morphine Derivatives
  • norcodeine
  • morphine-6-glucuronide
  • Morphine
  • Cytochrome P-450 CYP2D6
  • morphine-3-glucuronide
  • Codeine
  • normorphine