PBPK modeling of small molecules and biologics
Species Extrapolation / First in Human dose prediction
Parent-Metabolite Studies / Drug-Drug-Interaction
Pediatric Study Design – PIP/PDP support
Special Populations: Hepatic/Renal impairment / Obese / Elderly / (Pre)term neonates / Children / Pregnant women / more
Formulations / Meal effects
PBPK/PD, QSP as well as pathway, network and disease modeling
Model building blocks
Pre-parameterized whole-body PBPK models including detailed integrated GI tract for
with full flexibility for parameterization of (anthropo)metrics, anatomical and physiological properties, protein expression levels ETC.
Most important organs included. For each organ optional processes can be added:
Biliary tract included, enables enterohepatic cycling
Scaling can be used to change the biometrics of an existing individual, i.e. an adult model may be scaled to an infant model while maintaining/scaling all specific modifications
Database for population simulations with distributions of anatomical and physiological parameters for
The PK-Sim® library includes large-scale gene-expression data from publicly available sources which were downloaded, processed, stored and customized such that they can be directly utilized in PBPK model building. Public database which were imported are
Full ADME characterization of drugs including
and for large therapeutic molecules (e.g. antibodies)
Including a set of pre-parameterized standard compounds
Prediction models for tissue partition coefficients
Prediction models for cellular permeabilities and intestinal permeability
Parameter identification (PI)
A fully integrated PI Toolbox provides a straightforward means to adjust key model parameters automatically within user-defined ranges. It is possible to optimize multiple simulations, for example with different dose levels, and multiple observed data sets, simultaneously. A clear visualization of the optimization process and of the optimization results gives you full control and direct feedback whether the identification process was successful.
Sensitivity of PK-Parameters (AUC, CMax, …) vs. simulation parameters.
Because PBPK models can be complex and contain numerous input parameters, it would be useful to know which input parameters have the most impact on the output curves. The Sensitivity Analysis tool provides an answer to this question.
For a chosen simulation, the relative impact of selected - or all - input parameters on the PK parameters of the output curves is calculated and displayed. In addition, the input parameters can be ranked by their impact on a certain PK parameter of an output. Results of Sensitivity Analysis can be shown as:
Full transparency and full edit access to all structural model properties
If a human individual or population is selected the growth of the human individual(s) during the simulation time will be taken into account when choosing this option.
Based on the human growth and maturation functions available for most parameters in PK-Sim® (e.g. organ volumes, blood flow rates, organ composition, etc.) the parameters are updated along the time scale of the simulation. This is important for multiple drug administration to e.g. preterm and term neonates, for which the rapid changes in anatomical and physiological properties can influence the pharmacokinetics during the simulated study circle.
Import filters for
Import of SBML models
Editing of PK-Sim simulations to the detail of all parameters, structural elements, transports, reactions, events, and more.
Adding features to PK-Sim models, like tumors, complex molecular interactions, or non-standard drug applications
Display and editing of a simulation as tree or diagram
Result comparison charts
Simulation and building block comparison, exportable list of differences
Merging of building blocks from different simulations
Parameter identification and sensitivity analysis
Re-sending simulations back to PK-Sim for population simulation
Integrated working journal, sharable with PK-Sim, for documentation
Automatic tracking of changes made in a history log file
Export of simulated results as Excel file
Various formats of model exports and listings, like XML, Excel
Import of model parameters from Excel files
Import of model files in SBML format for QSP model building
Building models from scratch, like reaction pathways into a user-built spatial structure or for compartmental modeling
Option to select frequently accessed parameters as favorites