Background: Post-mortem redistribution (PMR) refers to changes in drug concentrations that can occur after death due to various processes such as passive diffusion from solid organs.1 Drug concentrations can also differ significantly depending on the site from which the specimen was taken.2 This can cause confusion for those trying to establish a cause of death as ‘toxic’ post-mortem concentrations of a drug may be mistakenly attributed to an overdose.
Aims: To develop a PBPK model for drugs which undergo post-mortem redistribution using PK-Sim® and MoBi® software.
Methods: PK Sim®, the PBPK modelling software developed by Bayer Technologies, was used to develop a model for therapeutic doses of Citalopram. The data was then exported to MoBi®, which allows for the dynamic modelling of biological processes and drug action. Using toxicology results of decedents who have not taken an overdose, i.e. blood concentrations are expected to be consistent with normal therapeutic doses, the accuracy of the model was tested. The actual concentrations should approximate the theoretical values predicted by the model. Once the model has been successfully validated, overdose scenarios for the drug can be explored.
Preliminary Results: A model simulating the post-mortem redistribution of Citalopram showed an increase in drug concentration over time when observed at central site as is expected for drugs susceptible to PMR.3 Further data is required to validate the model.
Conclusions: It is hoped that PBPK models can be designed to take some of the effects of PMR into account. If we can take steps towards quantifying the processes underlying PMR, we can provide more accurate interpretations of toxicology findings.
- Leikin, J. B. and W. A. Watson (2003). "Post-mortem toxicology: what the dead can and cannot tell us." J Toxicol Clin Toxicol 41(1): 47-56
- Prouty, R. W. and W. H. Anderson (1990). "The forensic science implications of site and temporal influences on postmortem blood-drug concentrations." J Forensic Sci 35(2): 243-70.
- Pelissier-Alicot, A. L., J. M. Gaulier, et al. (2003). "Mechanisms underlying postmortem redistribution of drugs: a review." J Anal Toxicol 27(8): 533-44.