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Review
. 2023 Jan 28;11(2):126.
doi: 10.3390/toxics11020126.

An Overview of Physiologically-Based Pharmacokinetic Models for Forensic Science

Kiara Fairman  1 , Me-Kyoung Choi  1 , Pavani Gonnabathula  1 , Annie Lumen  1 , Andrew Worth  2 , Alicia Paini  3 , Miao Li  1
Affiliations
Review

An Overview of Physiologically-Based Pharmacokinetic Models for Forensic Science

Kiara Fairman et al. Toxics. .

Abstract

A physiologically-based pharmacokinetic (PBPK) model represents the structural components of the body with physiologically relevant compartments connected via blood flow rates described by mathematical equations to determine drug disposition. PBPK models are used in the pharmaceutical sector for drug development, precision medicine, and the chemical industry to predict safe levels of exposure during the registration of chemical substances. However, one area of application where PBPK models have been scarcely used is forensic science. In this review, we give an overview of PBPK models successfully developed for several illicit drugs and environmental chemicals that could be applied for forensic interpretation, highlighting the gaps, uncertainties, and limitations.

Keywords: PBPK model; exposure; illicit drug; post-mortem redistribution; substance of abuse.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Comparison of a classical empirical compartmental model and a mechanistic physiologically-based pharmacokinetic (PBPK) model. (A) In the classical one-compartment model, a drug/chemical enters a central compartment, representing all tissues, by absorption, and is governed by the absorption rate constant (ka) while its elimination is described by the elimination rate constant (ke) (picture made using Microsoft ppt); (B) In the whole-body PBPK model, major organs/tissues are represented by compartments (boxes), connected by blood flows (venous and arterial blood pool; blue and red box, respectively), and flow is represented by the arrows (picture made using drawio.io).
Figure 2
Figure 2
Literature search strategy for forensic science and PBPK models. The steps of identification, screening, eligibility, and inclusion are depicted in this figure, with the relevant recorded hits per step.
Figure 3
Figure 3
Needs and potential for PBPK models in forensic science. A valid PBPK model can be used in interpretation of data and to fill gaps, providing supporting evidence in hearings and trials. The valid PBPK model could subsequentially be included in a PBPK model database, which would be valuable for other investigations.
See this image and copyright information in PMC

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