CSI Simcyp: How PBPK Models Provided Insight into a Fatal Drug Poisoning


Aarhus University scientists sought to determine the causes for toxic levels of medication in the case of an unintended fatal drug poisoning. They used mechanistic pharmacokinetic simulations to determine whether reduced metabolic capacity caused potentially toxic venlafaxine (VEN) concentrations in the poisoning victim. Pharmacokinetic simulations suggested that a lack of metabolic capacity due to missing CYP2C19 and CYP2D6 activity could have contributed to the fatal drug poisoning.

This fatal drug poisoning case shows the potential utility for using PBPK models to inform forensic toxicological assessments. Due to PBPK models’ ability to reflect a wide range of dosing scenarios and intrinsic/extrinsic patient factors, they are an ideal tool for helping determine the unsolved mechanisms behind fatal poisoning cases.