Assessing interindividual variability by Bayesian-PBPK modeling

The description of interindividual variability and the ADME-related sources of such variability (ADME: absorption, distribution, metabolization, excretion) is an essential element in clinical drug development to identify potentially relevant subgroups of non-responders or high-risk patients. The use of physiologically-based pharmacokinetic (PBPK) models supports a mechanistic understanding of the underlying ADME processes related to drug pharmacokinetics. In addition, the integration of Bayesian statistics into PBPK applications has allowed thorough assessment of interindividual variability and uncertainty of the pharmacokinetic behavior of drugs and underlying model parameters. Recent applications of Bayesian-PBPK approaches include subgroup stratification or improvement of the robustness of pharmacokinetic extrapolations.