Issue 3, 2019

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

Abstract

A whole-body permeability-rate-limited physiologically based pharmacokinetic (PBPK) model for cocaine was developed and adjusted with the pharmacokinetic data from studies with animals and reparametrized scaling to humans with the aim to predict the concentration–time profiles of the drug in blood and different tissues in humans. Estimated time course concentrations could be used as an interpretation tool by forensic toxicologists. The model estimations were compared successfully with pharmacokinetic parameters and time to peak for some effects reported in the literature. Once developed, the PBPK model was employed to predict the time course tissue concentrations reported in previous distribution studies introducing individualizing data. The heart and brain concentrations estimated by the model match adequately with the time and duration of some effects such as chronotropic and psychoactive effects, respectively. This work is the first attempt for employing PBPK modeling as a tool for forensic interpretation. Future modeling of other cocaine metabolite profiles or interaction when co-administered with other substances, such as alcohol, might be developed in the future.

Graphical abstract: Revisiting a physiologically based pharmacokinetic model for cocaine with a forensic scope

Supplementary files

Article information

Article type
Paper
Submitted
17 Nov 2018
Accepted
11 Feb 2019
First published
13 Mar 2019

Toxicol. Res., 2019,8, 432-446

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