Revisiting a physiologically based pharmacokinetic model for cocaine with a forensic scope

Area of Science:

• Pharmacokinetics
• Toxicology
• Computational Modeling

Background:

• Physiologically based pharmacokinetic (PBPK) models are crucial for understanding drug behavior in the body.
• Cocaine's pharmacokinetic profile and tissue distribution are complex and require sophisticated modeling for accurate prediction.
• Forensic toxicology often requires reliable tools to interpret drug concentrations and their associated effects.

Purpose of the Study:

• To develop and validate a whole-body, permeability-rate-limited PBPK model for cocaine.
• To predict cocaine concentration-time profiles in human blood and tissues.
• To establish PBPK modeling as a tool for forensic interpretation of cocaine exposure.

Main Methods:

• Developed a PBPK model for cocaine using animal pharmacokinetic data.
• Reparametrized the model for human scaling.
• Validated model predictions against literature data for pharmacokinetic parameters, time to peak effects, and tissue distribution.

Main Results:

• The PBPK model accurately predicted cocaine concentration-time profiles in blood and various tissues.
• Model estimations correlated well with reported pharmacokinetic parameters and time to peak effects.
• Predicted heart and brain cocaine concentrations corresponded with the onset and duration of chronotropic and psychoactive effects.

Conclusions:

• The developed PBPK model serves as a valuable tool for forensic toxicologists.
• This study represents the first application of PBPK modeling for forensic interpretation of cocaine.
• Future research could extend this model to include cocaine metabolites and drug interactions.