Pharmacokinetics is the study of the drug/xenobiotic-organism interaction, in particular the investigation of absorption, distribution, metabolism, excretion and toxicological (ADMETox) processes. In the past decade, considerable progress has been made with the use of computational approaches, in particular in the early stage of the drug discovery process. As a result, modelling and simulation is possible prior to any in vivo experiments.
Studying ADMETox profiles is used to identify and understand the physiological mechanisms that are most relevant from the point of view of pharmacokinetics or toxicokinetics. We aim at integrating metabolic and regulatory pathways on a mechanistic basis into physiologically-based pharmacokinetic models in order to analyze effect-related observables (biomarkers) on different levels. Moreover, we develop models to capture the effects of natural variability. The mathematical aspect include non-linear sensitivity analysis based on a recently developed adaptive semi-discretization in time of the associated PDE solved w.r.t. a time-dependend Galerkin ansatz space - integrating a multiscale approach for dimension reduction.
In cooperation with Computing in Technology (CiT), we develop the modular, application-specific and user-friendly virtual lab Medici-PK for modelling and simulation in pharmaco/kinetics/dynamics. We moreover cooperate with the Bundesinstitut für Risikobewertung (BfR), biotech companies, the Clinical Pharmacology (FU Berlin), the Zuse Institute Berlin (ZIB) and the Charite Berlin.
This project is supported by the Deutsche Forschungsgemeinschaft (DFG) within the Research Center MATHEON, the Bundesinstitut für Risikobewertung (BfR) and the International Max Planck Research School for Computational Biology and Scientific Computing IMPRS CBSC.