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 2023 (onsite): 27 - 31 March 2023. The schedule below is generic. For each PhD student year, the specific schedule will be sent via email to the participants.

The module will take place on site unless there is an unforeseen worsening of the COVID-19 pandemic.

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