Using physiology-based pharmacokinetic modelling for mechanistic analyses of drug action in disease and special populations

author: Tobias Kanacher, Bayer Technology Services GmbH
published: July 21, 2014,   recorded: May 2014,   views: 1602


Related Open Educational Resources

Related content

Report a problem or upload files

If you have found a problem with this lecture or would like to send us extra material, articles, exercises, etc., please use our ticket system to describe your request and upload the data.
Enter your e-mail into the 'Cc' field, and we will keep you updated with your request's status.
Lecture popularity: You need to login to cast your vote.


Inter-individual variability in clinical endpoints and occurrence of potentially severe adverse effects may hamper drug development at all phases of (pre-)clinical research. A comprehensive understanding of drug pharmacokinetics is hence of utmost importance in drug development.

Physiology-based pharmacokinetic (PBPK) models enable the mechanistic investigation of drug absorption, distribution, metabolism, and excretion at a mechanistic level of detail. This is because PBPK models describe processes governing drug pharmacokinetics based on a large amount of prior anatomical and physiological knowledge. Most notably, the computational models can be used to incorporate heterogeneous experimental data ranging from gene expression profiles at the cellular scale to physiological parameters at the whole-body level (e.g. organ volumes, blood flow rates, tissue composition) into one integrative modeling framework.

We show here how targeted experimental information can support the model-based investigation of patient-specific pharmacokinetics and moreover help to explain occurrence of adverse drug reactions. Genotype-specific PBPK models of codeine, simvastatin and pravastatin will be presented which include various protein-mediated processes underlying a particular pharmacokinetic behavior, respectively. We will then show how inter-individual variability in pharmacokinetics emerges as a consequence of a patient's genetic and phenotypic predisposition.

The methods presented outline how computational models together with targeted experimental data allow a mechanistic investigation of drug efficacy and even toxicity. Such integrative approaches may have significant implications for the development of individualized therapeutic strategies with a favorable risk-benefit profile in the future.

Link this page

Would you like to put a link to this lecture on your homepage?
Go ahead! Copy the HTML snippet !

Write your own review or comment:

make sure you have javascript enabled or clear this field: