Pharmacolibrary lightning talk TK

Created by Tomas Kulhanek

Physiologically based pharmacokinetic modeling with MODELICA and FMI: demo integration with PK database

Tomáš Kulhánek

VITO, Mol, Belgium

1^st Faculty of Medicine, Charles University, Prague, Czechia

standard Modelica language

Commercial tools:

Dymola,

, …

Open-source:

1. models

standard Modelica library 4.0.0

custom libraries for specific domains

Physiolibrary 3.0.0

www.physiolibrary.org

Physiomodel

Complex model of physiology in Modelica and Physiolibrary

https://physiomodel.org

blood-gas exchange

hemodynamics of cardiovascular system

respiration

co-simulation of multiple models via FMI in static web app with bodylight.js

i

https://egolem.online/demo/

new library: Pharmacolibrary 25.04 (beta)

connectors and components:

1-compartment model (in diagram)

equivalent 1-compartment model (in equations)

gentamicine

2-compartment model

midazolam

3-compartment model

fentanyl

Physiology based kinetic model

simulation PBK model

why in Modelica?

model of complex system may lead to implementation errors

A C Guyton, T G Coleman, H J Granger, Circulation: overall regulation, Annu Rev Physiol.1972;34:13-46.doi: 10.1146/annurev.ph.34.030172.000305.

Correction of schema after reimplementation in 2010

J.Kofránek, et al., Restoration of Guyton‘s Diagram for Regulation of the Circulation ...Physiol Res. 2010;59(6):897-908.doi: 10.33549/physiolres.931838.

comprehensibility

Frank-Starling law is  much more visible in component model - "force of the heart muscle depends on pressure of incoming blood". 

equivalent implementation in component and acausal modeling language

2.simulation

standard for simulation - FMI

Modelica tools support FMI

Matlab SIMULINK

FMPy for Python

Bodylight.js for web (model → FMI → emscripten → FMI JS with WebAssembly → + other components for charts, animation, markdown ...)

workflow - 1. export model to FMI unit 2. simulate in Python & fmpy & 3. get data from external data (PK-DB.com) 4. compare/fit/...

compile FMI unit to Webassembly & simulate FMI unit in web application (in-browser simulation)

powered by Bodylight.js: https://bodylight.physiome.cz 

web app simulation & interactive animation

final remarks

• Modeling library: https://github.com/creative-connections/Pharmacolibrary
• Web Simulation engine: https://bodylight.physiome.cz
• demo: https://egolem.online/pharma/ 
• SBML2Modelica https://bitbucket.org/mclab/sbml2modelica/src/master/
• make Modelica & FMI a Combine standard 

pharmacology & influence of physiology