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Abstract

Many cellular kinetic models of metabolic pathways and signal transduction networks have been established in the past. These can be used to study the impact of chemicals, e.g. drugs on the cellular behaviour, if the mechanism of this interaction is known. At the same time, whole-body pharmacokinetic models have been used for decades that - often in a lot of detail - describe the distribution dynamics and concentration profiles of drugs in the body after administration. However, an integration of these two scales has been lacking until recently. In this talk, a methodology to combine whole-body physiologically-based pharmacokinetic (PBPK) models with mechanistic intracellular models of signal transduction is presented. As a use case IFN-α administration is studied. A multi-scale model infers the time-resolved concentration of IFN-α arriving at the liver after intravenous injection while simultaneously estimating the effect of the respective dose on the intracellular signalling behaviour in the liver. 

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