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A fatal doxepin poisoning associated with a defective CYP2D6 genotype

Anna Koski1, Ilkka Ojanperä, Johanna Sistonen

  • 1Department of Forensic Medicine, University of Helsinki, Helsinki, Finland. anna.koski@iki.fi

The American Journal of Forensic Medicine and Pathology
|August 28, 2007
PubMed

Insights

Genetic variations in the CYP2D6 gene, which affects drug metabolism, may lead to fatal adverse effects. A postmortem toxicology case revealed a poor metabolizer phenotype, likely contributing to death from doxepin poisoning.

Area of Science:

  • Pharmacogenetics
  • Forensic Toxicology
  • Drug Metabolism

Background:

  • Polymorphisms in the CYP2D6 gene are implicated in adverse drug reactions.
  • Investigating postmortem toxicology cases involving CYP2D6 substrates is crucial for understanding fatal poisonings.

Observation:

  • A fatal doxepin poisoning case with an undetermined manner of death was analyzed.
  • The individual possessed a nonfunctional CYP2D6 genotype (*3/*4), indicating a poor metabolizer phenotype.
  • Doxepin and nordoxepin concentrations were measured, with a low doxepin/nordoxepin ratio suggesting impaired metabolism.

Findings:

  • The patient's CYP2D6 genotype (*3/*4) indicated a complete absence of enzyme activity.
  • Elevated N-desmethylmetabolite levels were inconsistent with acute intoxication.
  • The defective genotype is strongly suspected to have contributed to the fatal outcome, possibly due to repeated high doxepin dosage.

Implications:

  • Pharmacogenetic analysis in postmortem settings can provide critical insights into the cause of death.
  • This case highlights the importance of considering genetic factors in fatal drug poisonings.
  • Understanding CYP2D6 genotype-phenotype relationships is vital for forensic toxicology and clinical practice.

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