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Enabling Risk-Based Decisions with Pharmaco- and Toxicokinetic Models while Addressing Transparency and Reproducibility
Citation:
Wambaugh, J. Enabling Risk-Based Decisions with Pharmaco- and Toxicokinetic Models while Addressing Transparency and Reproducibility. SOT, Nashville, TN, March 19 - 23, 2023. https://doi.org/10.23645/epacomptox.22280572
Impact/Purpose:
A PowerPoint presentation has been prepared by John Wambaugh for presentation to the Society of Toxicology annual meeting as part of a short workshop on “Crucial role of Physiologically-Based (Pharmaco-)kinetic (PBK) Modelling in Human Health Risk Assessment in Different Sectors”. The presentation is entitled “Enabling Risk-Based Decisions with Pharmaco- and Toxicokinetic Models while Addressing Transparency and Reproducibility”.
Description:
Pharmacokinetics/Toxicokinetics enables quantitative characterization of chemical risk by allowing insight into the dose-response relationship. However, some aspects of kinetics are chemical-specific and require parameters and other features that must be derived from data and/or structure-based predictions. Models and their parameters are typically vetted through the scientific peer-review process which, while important, has been shown in many cases to be insufficient for risk evaluators (McLanahan et al., 2012). This presentation will compare and contrast the issues for pharmaceuticals and chemicals in commerce. We will then investigate both 1) model reporting templates and 2) "generic" models with consistent form and parameterization as alternatives that enable transparency and reproducibility to better inform regulatory decision making. Traditional approaches to developing PBK models were focused on single chemicals, with chemical-specific consideration of key physiology - these models are resource-intensive and often dependent upon data derived from animals. More recently generic PBK models with standardized physiologies that depend on in vitro measurements have emerged as a higher throughput alternative to traditional PBK.
URLs/Downloads:
DOI: Enabling Risk-Based Decisions with Pharmaco- and Toxicokinetic Models while Addressing Transparency and Reproducibility
SOT2023-WAMBAUGH-TRANSPARENCYFORTK-2.PDF (PDF, NA pp, 3277.075 KB, about PDF)