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An animal model of postmortem amitriptyline redistribution
T Hilberg1, A Bugge, K M Beylich
1National Institute of Forensic Toxicology, Oslo, Norway.
Journal of Forensic Sciences
|January 1, 1993
Summary
This study developed a rat model to investigate postmortem drug changes. Amitriptyline concentrations in heart blood and peripheral blood increased significantly after death, mimicking human patterns.
Area of Science:
- Forensic Toxicology
- Pharmacokinetics
- Animal Models
Background:
- Postmortem drug redistribution is a significant challenge in forensic toxicology.
- Understanding drug concentration changes after death is crucial for accurate interpretation of toxicological findings.
Purpose of the Study:
- To develop and validate an experimental rat model to study postmortem changes in amitriptyline (AMI) and nortriptyline (NOR) concentrations.
- To investigate the distribution and redistribution of AMI and its metabolite NOR in blood and tissues postmortem.
Main Methods:
- An acute overdose rat model was established using amitriptyline.
- Blood and tissue samples were collected at various time points postmortem (0.1 to 96 hours).
- High-performance liquid chromatography was used to quantify drug concentrations.
Main Results:
- Amitriptyline concentrations increased significantly in heart blood and peripheral blood postmortem.
- The post/antemortem concentration ratio for AMI showed an exponential rise in peripheral blood over time.
- Liver tissues showed high, variable concentrations, while lung concentrations declined postmortem.
Conclusions:
- The developed rat model effectively mimics human postmortem drug concentration changes.
- Mechanisms include diffusion from the GI tract and release from tissues like lungs.
- This model aids in understanding postmortem redistribution for improved forensic analysis.