Hands-On Demonstrations of the Physiology-Based Pharmacokinetic Software, PK-Sim®
Willmann, Stefan, Wolfgang Weiss, Andrea N. Edginton
Bayer Technology Services GmbH, Germany
PK-Sim(R) is a software tool for physiology-based pharmacokinetic whole-body modelling in laboratory animals (mouse, rat, dog) and humans. It is designed for pre-clinical and clinical use in the pharmaceutical research and development environment. Two modules included in the PK-Sim(R) software will be the focus of the presentation. In the PK-Sim(R) population module, the pharmacokinetic variability of a drug can be tested a priori in a virtual human population with a user-defined gender-, age-, height-, and weight distribution. A Monte-Carlo process is used to create virtual individuals matching the user-defined parameters. The PK-Pop module contains a large database of relevant anthropometric and physiological parameters. A sophisticated algorithm accounts for cross-correlations in the variabilities of different physiological parameters via scaling laws and thus ensures that only reasonable representatives of living humans are created within the age range of 0 to 80 years. All variabilities are included in the model and do not have to be user-defined thus reducing the expected user-input parameters. The second module “Clearance Scaling” uses validated models to scale renal and hepatic clearance from adults to children of all ages. Integration with the population module allows for a determination of the pharmacokinetic variability expected in a young population.
In this software demonstration we provide an overview of PK-Sim(R)’s capabilities to simulate the pharmacokinetic behaviour of chemical compounds in different populations including children, adults, and elderly. Applications to the different stages of clinical development will be discussed.