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Oxycodone findings and CYP2D6 function in postmortem cases
Gerd Jakobsson1, Ronja Larsson2, Lucia Pellè3
1Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, 58758 Linkoping, Sweden; Division of Drug Research, Department of Biomedical and Clinical Sciences, Faculty of Health and Science, Linkoping University, 58183 Linkoping, Sweden.
Forensic Science International. Genetics
|April 2, 2021
Summary
Genetic variations in CYP2D6 enzyme activity affect oxycodone levels. Genotyping helps interpret postmortem drug concentrations and time of intake, but requires phenotype knowledge for accuracy.
Area of Science:
- Pharmacogenomics
- Forensic Toxicology
- Clinical Chemistry
Background:
- Genetic variations influence drug metabolism, impacting clinical response and forensic interpretation.
- CYP2D6 enzyme activity varies significantly among individuals, affecting oxycodone pharmacokinetics.
- Accurate interpretation of postmortem drug concentrations is crucial for determining cause and time of death.
Purpose of the Study:
- To investigate the frequency of CYP2D6 phenotypes in postmortem cases with oxycodone presence.
- To determine if CYP2D6 activity correlates with cause of death, drug concentration, or metabolic ratios.
- To assess the utility of CYP2D6 genotyping in forensic interpretation of oxycodone intake.
Main Methods:
- Genotyping for CYP2D6*3, *4, *6 via pyrosequencing and *5 copy number variation via digital droplet PCR.
- Quantification of oxycodone and its metabolites (noroxycodone, oxymorphone, noroxymorphone) using LC-MS/MS.
- Categorization of cases by cause of death and analysis of CYP2D6 phenotype distribution.
Main Results:
- Poor and intermediate CYP2D6 metabolizers exhibited significantly higher oxycodone and noroxycodone concentrations.
- CYP2D6 phenotypes were evenly distributed across different cause of death groups.
- The oxymorphone/oxycodone ratio correlated with CYP2D6 activity in non-intoxication deaths, with a ratio <0.075 indicating acute intake.
Conclusions:
- CYP2D6 genotyping aids in interpreting postmortem oxycodone concentrations and metabolic ratios.
- While the oxymorphone/oxycodone ratio shows sensitivity for acute oxycodone intoxication, high specificity requires knowing the individual's CYP2D6 phenotype.
- Genotyping is essential for accurate forensic interpretation and should complement ratio-based analyses.