You are here:
Can pharmacokinetic modelling keep up with risk assessment in the 21st Century?
Citation:
Wambaugh, J. Can pharmacokinetic modelling keep up with risk assessment in the 21st Century? Society of Toxicology annual meeting, San Antonio,TX, March 11 - 15, 2018. https://doi.org/10.23645/epacomptox.7346765
Impact/Purpose:
Can pharmacokinetic modelling keep up with risk assessment in the 21st Century? Yes, but in vitro and in silico tools for toxicology require chemical-specific toxicokinetics (TK). High throughput TK (HTTK) methods work well enough but require analytical chemistry and that the chemical is amenable to in vitro testing. In silico HTTK methods offer path forward. Model reliability continues to be an issue, but generic models offer a path forward.
Description:
In order to evaluate a chemical-specific TK model for “chemical x” you can compare the predictions to in vivo measured data. However, we do not typically have TK data. We can parameterize a generic TK model, and evaluate that model for as many chemicals as we do have data. Generic PBTK models based on HTTK seem to increase correlation between in vitro bioactivity and in vivo effects. Using PBTK to predict tissue concentrations does better than using administered dose (or PBTK for random chemical).
URLs/Downloads:
DOI: Can pharmacokinetic modelling keep up with risk assessment in the 21st Century?
WAMBAUGH-SOT2018-MONMARCH12-FUTUREPK.PDF (PDF, NA pp, 318.155 KB, about PDF)