Systems Theory and Automatic Control

Systems and Control Seminars for the winter semester 10/11

Application of integrated multi-scale models to pharmaceutical research and development


Dr. Lars Küpfer
Systems Biology and Computational Solutions
Bayer Technology Services GmbH
51368 Leverkusen, E 41

Time and Place

The presentation will be given on Wednesday April 6, 2011, at 5 p.m. in building 07, room 208, Campus Universitätsplatz


Computational models play an increasing role in pharmaceutical research and development, since they offer an efficient way for storing, representing and analyzing experimental data at each stage of (pre-)clinical development. Physiologically-based pharmacokinetic (PBPK) models are a special form of pharmacokinetic models which represent the processes underlying the distribution of a substance within the human body mechanistically at a high level of detail. Based on generic drug distribution models and extensive collections of physiological parameters they thus enable a comprehensive simulation of drug pharmacokinetics at the whole-body scale. Moreover, structural refinements such as metabolization processes or active transport can easily be introduced into the basic PBPK models such that structural hypotheses can be evaluated.

Using different exemplary case studies we show here how computational models allow the investigation of mechanisms governing a specific pharmacokinetic behavior. Simultaneous consideration of a drug's modes of action at the cellular level enables construction of integrated multi-scale models based on which dose-effect relationships can be investigated from a systems perspective. Such multi-scale models have amongst others been used for the correlation of genetic predisposition in a patient subgroup with clinical endpoints. Computational models thereby significantly support assessment of crucial points in drug R&D such as (1) a rigorous evaluation of drug efficacy at an early phase of clinical development, (2) avoidance of adverse effects and (3) development of individualized therapeutic designs.

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Information about the Speaker

Lars Kuepfer is a scientist in the group "Systems Biology and Computational Solutions" of Bayer Technology Services GmbH in Leverkusen. He studied chemical engineering at the TH Karlsruhe, RWTH Aachen and Carnegie Mellon University, Pittsburgh, and received his Ph.D. degree from ETH Zurich. In his thesis, Lars Kuepfer analyzed metabolic and regulatory principles in yeast based on computational models. In his current position, he works on pharmacokinetic and pharmacodynamic modeling of novel drug candidates thereby supporting decision making along the pharma development process. Lars Kuepfer's main research interests are in the area of pharmacogenomics, metabolic modeling and system identification.

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