Pharmacolibrary

Pharmacolibrary is a reusable Modelica library unifying pharmacokinetic, pharmacodynamic, toxicokinetic, toxicodynamic, and pharmacogenomic constructs with standardized pharmacological terminology, units, and acausal connectors.

Instruction

• download Pharmacolibrary, e.g. complete development repository

git clone .../Pharmacolibrary.git

or just last version

• use Modelica tool, e.g. OpenModelica[1] or Dymola[2]
  • inside the tool, File -> Open Model/Library File
  • select Pharmacolibrary/package.mo
• Open Examples
  • each model in Examples package shows some feature on concrete model of drug pharmacokinetic, pharmacodynamic and pharmacogenomic. Sample model with complex physiologically based model is also shown.

[1] OpenModelica: https://www.openmodelica.org
[2] Dymola:https://www.3ds.com/products/catia/dymola

Modeling

The following acausal connectors are available and reused in library:

domain	potential variables	flow variables	stream variables	connector definition	icons
chemical concentration	mass concentration	mass flow rate		Pharmacolibrary.Interfaces  ConcentrationPort, ConcentrationPort_a, ConcentrationPort_b
volumetric flow	pressure	volume flow rate	mass concentration	Pharmacolibrary.Interfaces  FlowPort, FlowPort_a, FlowPort_b

Pharmacolibrary focuses it's components into these main pharmacological phenomena:

Library Domain	Description
	Pharmacokinetic Pharmacokinetic (PK) can model kinetic and toxicokinetic in terms of absorption, distribution, metabolism, elimination of a drug. 2 main approaches exists: compartmental models (1-compartment, 2-compartment, multi compartment models) - neglects cardiac output and simplifies tissue distribution. Most commonly published with these parameters: m [mg] drug dose administered (Dose component) F [0-1] bioavailability (Dose component) Vd [l] volume of distribution (Compartment component) Cl [l/min] elimination/intercompartmental clearance (Elimination component) PBPK models combines compartments with physiological based models, e.g. circulation.
	Pharmacodynamic Pharmacodynamic (PD) can model dynamic effect of a drug on target tissue or cells. Main components are Effect (LinearEffect, EmaxEffect,SigmoidEmaxEffect) that translates from drug concentration into a generic effect quantity.
	Pharmacogenomic Pharmacogenomic (PGx) can model dynamic influence of Genotype/Phenotype by altering parameters of PK/PD absorption, clearance, metabolism and effect.
Drugs	Drugs Drugs library contains selected PK, PD, PG models organized by ATC index using 1'st level fourteen main anatomical/pharmacological groups and 2nd level pharmacological or therapeutic groups. Subsequent groups are not used and direct ATC code with drug name as package contains various basic or advanced models.

Simulation outside Modelica - integration to computational workflow in Python

• got so sim directory

cd sim/

• and prepare virtual env in Python python -m venv venv source venv/bin/activate

  * install requirements as specified in `requirements.txt` file
```bash
pip install -r requirements.txt

• start jupyter

jupyter lab

• jupyter opens in a browser interactive interface, open notebook PK_2C_IVMidazolam.ipynb
• the demo contains exported 2-compartment model of Midazolam administered intravenously in FMI, its usage with fmpy library and integration with pharmacokinetic database containing growing number of human and machine readable data of drugs from https://pk-db.com

Simulator

Live sample web simulator at: https://egolem.online/pharma translated by Bodylight.js-FMU-Compiler and powered by bodylight.js