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George Loizou, Alex Hogg and Kevin McNally
HSE Science and Research Centre
R-Vis
An Open Access PBPK Modelling Platform
Aims and Objectives
• Further develop R-Vis, a prototype application for the analysis of structure and performance of physiologically based pharmacokinetic
(PBPK), and other models, written in the free, open source syntax, R
• Provide a common, transparent and independently auditable, free-to-use platform
• Provide a labour-saving application that also shifts emphasis away from mathematics and programming to mechanistic toxicology
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
A PBPK Model
R Syntax Viewed in RStudio
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Home Page
Import Model
LRI – – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Plotter
Select Parameters and Outputs
LRI – R-Vis: An Open Access PBPK Modelling Platform
Parameters (constants)• Anatomical
• Physiological
• Metabolic
• Physicochemical
Outputs (calculated values)• Rates of uptake
• Dermal, oral, inhalation
• Concentrations:
• Venous, arterial, plasma, red blood cells
• Organs and tissues
• Urinary excretion
• exhalation
Plotter
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Plotter
Plot Output
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Plotter
Multiple Outputs
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Evidence
Importing Data
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Evidence
Tweaking Parameters
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Evidence
Tweaking Parameters Using Ranges
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Good Modelling Practice
Model Structure and Biological Plausibility
22/11/2019LRI – PRESENTATION TITLE
Evaluating Variability and Uncertainty
LRI – R-Vis: An Open Access PBPK Modelling Platform
Morris Test – Elementary Parameter Screening
Sensitivity Analysis
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Extended Fourier Amplitude Sensitivity Test - eFAST
Global Sensitivity Analysis
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – PRESENTATION TITLE
LRI – R-Vis: An Open Access PBPK Modelling Platform
Parameter configurations available to all modules
Shared State
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Markov Chain Monte Carlo Sampling
Parameter Estimation – Reverse Dosimetry
LRI – R-Vis: An Open Access PBPK Modelling Platform
Bayesian Inference – Prior Knowledge
LRI – PRESENTATION TITLE
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Probabilistic Modelling
Monte Carlo Sampling
LRI – R-Vis: An Open Access PBPK Modelling Platform
Incorporating Inter-Individual Differences
LRI – R-Vis: An Open Access PBPK Modelling Platform
Incorporating Inter-Individual Differences: Organs/Tissue Distributions
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Generating Virtual Humans
LRI – R-Vis: An Open Access PBPK Modelling Platform
Settings – User Preferences
Appearance
LRI – R-Vis: An Open Access PBPK Modelling Platform
LRI – R-Vis: An Open Access PBPK Modelling Platform
Acknowledgements
• Alex Hogg – Programmer
• Kevin McNally – Statistical/Mathematical Modeller
• Cefic-LRI
LRI – R-Vis: An Open Access PBPK Modelling Platform
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Tel +32 2 436 9415 – lri@cefic.be
www. cefic-lri.org
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European Chemical Industry Council (Cefic)
Rue Belliard 40
1040 Brussels
Tel +32 2 436 93 00
www.cefic-lri.org
LRI SECRETARIAT
THE VOICE OF THE CHEMICAL INDUSTRY IN EUROPE
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