New issue

Have a question about this project? Sign up for a free GitHub account to open an issue and contact its maintainers and the community.

By clicking “Sign up for GitHub”, you agree to our terms of service and privacy statement. We’ll occasionally send you account related emails.

Already on GitHub? Sign in to your account

A generic whole body physiologically based pharmacokinetic model for therapeutic proteins in PK-Sim #152

msevestre opened this Issue Dec 13, 2017 · 0 comments


None yet
1 participant

msevestre commented Dec 13, 2017

Christoph Niederalt, Lars Kuepfer, Juri Solodenko, Thomas Eissing, Hans-Ulrich Siegmund, Michael Block, Stefan Willmann, Jörg Lippert


Proteins are an increasingly important class of drugs used as therapeutic as well as diagnostic agents. A generic physiologically based pharmacokinetic (PBPK) model was developed in order to represent at whole body level the fundamental mechanisms driving the distribution and clearance of large molecules like therapeutic proteins. The model was built as an extension of the PK-Sim model for small molecules incorporating (i) the two-pore formalism for drug extravasation from blood plasma to interstitial space, (ii) lymph flow, (iii) endosomal clearance and (iv) protection from endosomal clearance by neonatal Fc receptor (FcRn) mediated recycling as especially relevant for antibodies. For model development and evaluation, PK data was used for compounds with a wide range of solute radii. The model supports the integration of knowledge gained during all development phases of therapeutic proteins, enables translation from pre-clinical species to human and allows predictions of tissue concentration profiles which are of relevance for the analysis of on-target pharmacodynamic effects as well as off-target toxicity. The current implementation of the model replaces the generic protein PBPK model available in PK-Sim since version 4.2 and becomes part of the Open Systems Pharmacology Suite.


Physiologically based pharmacokinetic modelling PBPK Therapeutic proteins Antibodies Biologics

Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment