Sensitivity analysis (SA) is an essential tool for modelers to understand the influence of model parameters on model outputs. It is also increasingly used in developing and assessing physiologically based kinetic (PBK) models. For instance, several studies have applied global SA to reduce the computational burden in the Bayesian Markov chain Monte Carlo-based calibration process PBK models. Although several SA algorithms and software packages are available, no comprehensive software package exists that allows users to seamlessly solve differential equations in a PBK model, conduct and visualize SA results, and discriminate between the non-influential model parameters that can be fixed and those that need calibration.
Traditionally, the solution to reduce parameter dimensionality in a physiologically-based pharmacokinetic (PBPK) model is through expert judgment. However, this approach may lead to bias in parameter estimates and model predictions if important parameters are fixed at uncertain or inappropriate values. The purpose of this study was to explore the application of global sensitivity analysis (GSA) to ascertain which parameters in the PBPK model are non-influential, and therefore can be assigned fixed values in Bayesian parameter estimation with minimal bias.