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Related Experiment Videos

Discrepancy between CYP2D6 phenotype and genotype derived from post-mortem dextromethorphan blood level.

B Bailey1, R Daneman, N Daneman

  • 1Department of Pediatrics, Division of Clinical Pharmacology and Toxicology, H¿opital Ste-Justine, 3175 Cote St. Catherine, Montr¿eal, Qu¿ebec, Canada. baileyb@med.umontreal.ca

Forensic Science International
|May 10, 2000
PubMed
Summary

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A toddler died after a therapeutic dose of dextromethorphan. Post-mortem analysis revealed high drug levels, suggesting a potential issue with drug metabolism despite a fast CYP2D6 genotype.

Area of Science:

  • Pharmacology
  • Toxicology
  • Genetics

Background:

  • Dextromethorphan is a common antitussive agent.
  • Therapeutic drug monitoring is crucial, especially in pediatric cases.
  • Cytochrome P450 enzymes, particularly CYP2D6, play a key role in dextromethorphan metabolism.

Observation:

  • A 20-month-old toddler experienced a fatal outcome following therapeutic dextromethorphan administration.
  • Post-mortem blood analysis revealed significantly elevated dextromethorphan and dextrorphan concentrations.
  • The toddler presented with bronchopneumonia, though bacterial cultures were negative.

Findings:

  • The dextromethorphan/dextrorphan ratio suggested a slow CYP2D6 metabolizer phenotype.
  • However, genetic analysis indicated the toddler possessed a fast CYP2D6 metabolizer genotype.

Related Experiment Videos

  • Post-mortem drug redistribution studies in rats did not explain the high observed dextromethorphan levels.

    • Implications:

    • Discrepancies between phenotypic and genotypic drug metabolism assessments can occur.
    • Post-mortem CYP450 phenotypes derived from blood levels require cautious interpretation.
    • Genotype analysis is recommended for confirmation when interpreting post-mortem drug metabolism data.