An Overview of Physiologically-Based Pharmacokinetic Models for Forensic Science

Author: mycolabadmin
1/28/2023
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Summary

This review examines how mathematical models that predict how drugs and chemicals move through the body could be better used in forensic science to help explain cause of death and interpret toxicology evidence. Currently, only a few such models have been specifically developed for forensic purposes, though many exist for common drugs like opioids, cocaine, and alcohol. A major challenge is accounting for how drug concentrations change after death, which can make it harder to determine what the concentration was when the person died.

Background

Physiologically-based pharmacokinetic (PBPK) models represent the body’s structural components with physiologically relevant compartments to determine drug disposition. While PBPK models are widely used in pharmaceutical development and chemical risk assessment, their application in forensic science has been limited despite potential utility for interpreting forensic toxicology evidence.

Objective

This review provides an overview of PBPK models developed for illicit drugs and environmental chemicals that could be applied for forensic interpretation. The review highlights available models, their applications in different exposure scenarios (acute, short-term, and long-term), and identifies gaps, uncertainties, and limitations in current forensic applications.

Results

Two articles explicitly developed PBPK models for forensic purposes (morphine and cocaine). Additional models were identified for opioids, psychostimulants, psychedelics (psilocybin, mitragynine), alcohol, and environmental chemicals (PFAS, cyanide, TCE). Post-mortem redistribution phenomena and organ-specific toxicity considerations were identified as critical factors requiring integration into forensic PBPK models.

Conclusion

PBPK models have significant potential for forensic applications in predicting drug and chemical concentrations in blood and tissues over time, though substantial work remains to adapt existing models for forensic contexts. Key challenges include incorporating post-mortem redistribution phenomena, validating models with post-mortem tissue data, and standardizing forensic applications across different exposure scenarios and drug classes.

Published in:Toxics,
Study Type:Review,
Source: PMID: 36851001