Bayesian inference informed by parameter subset selection for a minimal PBPK brain model

Source abstract

Physiologically based pharmacokinetic (PBPK) models use a mechanistic approach to delineate the processes of the absorption, distribution, metabolism and excretion of biological substances in various species. These models generally comprise coupled systems of ordinary differential equations involving multiple states and a moderate to a large number of parameters. Such models contain compartments corresponding to various organs or tissues in the body. Before employing the models for treatment, the quantification of uncertainties for the parameters, based on a priori information or data for a specific response, is necessary. This requires the determination of identifiable parameters, which are uniquely determined by data, and uncertainty analysis based on frequentist or Bayesian inference. We introduce a strategy to integrate parameter subset selection, based on identifiability analysis, with Bayesian inference. This approach further refines the subset of identifiable parameters, quantifies parameter and response uncertainties, enhances model prediction and reduces computational cost. This article is part of the theme issue ‘Uncertainty quantification for healthcare and biological systems (Part 1)’.