A2: Introduction to physiologically-based pharmacokinetics
The module introduces the fundamental concepts of physiologically-based pharmacokinetic (PBPK) modeling. The overall theme of the module is to see PBPK modeling as a way to integrate prior knowledge on physiological processes, anatomical spaces and drug-specific properties into the modeling process and to generate questions (the more questions we ask, the better we are prepared), and test hypotheses.
The module includes mathematical models of principle absorption, distribution, metabolism and excretion (ADME) processes, whole-body PBPK models, lumping of PBPK models and its link to classical compartment models (thereby establishing the link to the A1 module Introduction to pharmacokinetics and pharmacodynamics (PK/PD), models to predict inter-individual variability and to integrate covariates (thereby establishing the link to the A3 module Introduction to population analysis.
Frequency: Every year in March/April.
Language: English
Module in 2024 (onsite): 18 - 22 March 2024. The schedule below is generic. For each PhD student year, the specific schedule will be sent via email to the participants.
Illustrative schedule
| Time | Monday | Tuesday | Wednesday | Thursday | Friday |
|---|---|---|---|---|---|
| 8:45 – 10:45 | Introduction to PBPK modeling | Important ADME sub-processes, hepatic metabolisms and renal excretion | Lumping of PBPK models & its relation to classical compartmental models | Inter-individual variability, extrapolation to children & covariate modeling | Introduction to PBPK modeling of monoclonal antibodies |
| 30 min | Coffee break | ||||
| 11:15 - 13:00 | Introduction to PBPK modeling (con't) | Hands-on | Hands-on | Hands-on | Hands-on |
| 60 min | Lunch break | ||||
| 14:00 - 15:30 | Tissue model and whole body PBPK models for small molecule drugs | A priori prediction of tissue partitioning | Guest lecture: Dr. Andreas Reichel, Bayer AG, Project meeting simulation | PK-Sim (Bayer AG): Introduction and hands-on | PBPK modeling in drug discovery, development and regulatory science |
| 15 min | Coffee break | ||||
| 15:45 - 17:00 | Hands-on | Hands-on (con't) | Project meeting simulation (con't) | Hands-on with PK-Sim (con't) | |
| Evening | Social Event (joint event of A1+A2 module) | ||||
Contributions:
- Prof. Wilhelm Huisinga; theoretical lectures
- PharMetrX PhD students (2nd/3rd year); hands-on exercises
- External contributions by our faculty members
Hard- and software
- Please bring your own laptop.
- MATLAB® (The MathWorks), will be provided during the module.
- PK-Sim available for download at Open Systems Pharmacology Suite.
Literature
- Detailed references will be provided during the course.
- W. Huisinga et al, Modeling inter-individual variability in physiologically-based pharmacokinetics and its link to mechanistic covariate modeling, CPT: Pharmacometrics & Systems Pharmacology, 1 (2012), e4 (incl. online supplement on parameter values and matlab files)
- M. Rowland et al, Physiologically-Based Pharmacokinetics in Drug Development and Regulatory Science, Annual Review of Pharmacology and Toxicology, 51 (2011), pp. 45-73