CAS Seminar

Karina Claassen

(Jacobs University / Bayer Technology Services GmbH)

"Development of a physiologically-based model with an integrated regulatory and excitable cardiovascular system"

Date: Wed, November 30, 2011
Time: 11:15
Place: Research I Seminar room

Abstract: The talk will give a short introduction to whole body physiologically based pharmacokinetic (WB-PBPK) modeling. A PBPK approach in the context of the PhD Thesis “Development of a Physiologically-based Model with a regulatory and excitable cardiovascular system“ will be shown in detail and first results will be discussed.

WB-PBPK modeling is a mechanistic, computational method to make predictions of the absorption, distribution, metabolization and excretion (ADME) processes in laboratory animals and humans. This method is based on detailed knowledge about the physical and physiological processes affecting the pharmacokinetics of a drug. The general idea of PBPK modeling is to represent the organs of an organism by a number of physiologically relevant compartments. To describe the drug distribution in the body, these compartments are mathematically connected by means of mass-balance equations (ODE’s) that describe the transport of the drug.

The development of drugs regulating the cardiovascular system (CVS) by the pharmaceutical industry is of high relevance, because cardiovascular disease (CVD) is a global epidemic. To get a better knowledge about responsible processes and to support a cost-effective development, modeling and simulation techniques are well accepted and very potent methods.

The PhD thesis is aimed to integrate a cardiovascular model into a whole body WB-PBPK model to establish a mechanistic representation of the regulatory character of CVS under different physiological conditions. After a short physiological introduction the first steps in the development of a regulatory CVS model and its integration into a WB PBPK model will be shown. One of the systems interacting with the CVS is the Renin-Angiotensin-Aldosterone-system (RAAS). Therefore a separately developed model of the RAAS, and the integration of it into the WB PBPK model will be presented, even as the inclusion of a first RAAS blocking drug.