New Compartmental Gastro-Intestinal Model

With the aim of providing a tool for predicting absorption of orally administered drugs more precisely - including drug-drug interactions within the gut wall and the effects of active transport and gut wall metabolism - the existing absorption model of PK-Sim® was revised. This revised model reflects more detailed knowledge of human gastrointestinal physiology including fluid secretion and absorption and comprises an elaborate representation of the intestinal mucosa.

With this detailed representation of the mucosa, the model is optimally equipped to support the development of mechanistic models of active transport processes and gut wall metabolism.

Additionally, the revised model for GI transit and absorption was successfully integrated with dissolution functions of the Weibull type. In combination with biorelevant dissolution testing, the extended model represents a powerful tool enabling users to  predict the in vivo performance of drugs based on physicochemical parameters as well as in vitro properties at various stages of drug development. Especially in the area of formulation development, the model can be applied to quickly and cost-effectively predict how different dosage forms affect the in vivo outcome as well as to identify target release profiles for in vitro tests.

Besides these state-of-the-art features, the new model further allows to consider phenomena like intra-lumenal metabolization, micelle formation and degradation, or description of special experimental setups like bile-duct canulation or charcoal co-administration in a straight-forward mechansitic approach.

Features of the new model for GI transit and Absorption include:

  • 12 compartments representing the lumen of different segments, with spatially varying properties (surface area, pH)
  • Physiological liquid volumes (Liquid) and drug in solution (DIS) for each individual compartment
  • Solid dosage form (SDF, e.g. Tablet) is transported along the GI tract independently
  • Once released from SDF and dissolved according to the dissolution function, the drug is transferred from the SDF species to the DIS species
  • 11 compartments representing the intestinal mucosa (subdivided into enterocytes, interstitial and vascular space)

The new model is an integral part of the release of our new platform including PK-Sim® 5 and MoBi® 3. More details can be found in the publications linked below:

Thelen K, Coboeken, K, Willmann S, Burghaus R, Dressman JB, Lippert J. 
Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, Part 1: Oral solutions.
J Pharm Sci. 2011 Dec;100(12):5324-45. doi: 10.1002/jps.22726. Epub 2011 Oct 12.

Thelen K, Coboeken K, Willmann S, Dressman JB, Lippert J.
Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, Part 2: Extension to describe performance of solid dosage forms.
J Pharm Sci. 2011 Nov 28. doi: 10.1002/jps.22825. [Epub ahead of print]


April 12, 2017

Two new publications regarding PBPK modeling! : A pregnancy PBPK model has been developed, and evaluated for renally cleared drugs.

» More

March 28, 2017

Published in npj Systems Biology and Applications: Translational learning from clinical studies predicts drug pharmacokinetics across patient populations

» More

December 19, 2016

New publications regarding PBPK modeling: Elderly, Isoniazid, DDI and Diabetes. In addition: A white paper regarding good practices in drug discovery and development

» More

» All News

October 14, 2017

ACoP8 Conference, October 15-18 2017 in Florida

» More

June 25, 2017

14th European ISSX Meeting, June 26-29 2017 in Cologne

» More

June 05, 2017

PAGE Meeting 2017, June 06-09, Budapest, Hungary

» More

» All Events