Predicting nonlinear relationships between external and internal concentrations with physiologically based pharmacokinetic modeling.

ABSTRACT: Although external concentrations are more readily quantified and often used as the metric for regulating and mitigating exposures to environmental chemicals, the toxicological response to an environmental chemical is more directly related to its internal concentrations than the external concentration. The processes of absorption, distribution, metabolism, and excretion (ADME) determine the quantitative relationship between the external and internal concentrations, and these processes are often susceptible to saturation at high concentrations, which can lead to nonlinear changes in internal concentrations that deviate from proportionality. Using generic physiologically-based pharmacokinetic (PBPK) models, we explored how saturable absorption or clearance influence the shape of the internal

SUBMITTER: Hoer D 

PROVIDER: S-EPMC10519136 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature