Quantitative Systems Pharmacology and Physiologically-Based Pharmacokinetic Modeling With mrgsolve: A Hands-On...

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Computational Biology
• Systems Pharmacology

Background:

• Physiologically-based pharmacokinetic (PBPK) and quantitative systems pharmacology (QSP) models are crucial for drug development and understanding biological systems.
• Simulation tools are essential for analyzing these complex models.
• The R programming environment offers a flexible platform for data analysis and modeling.

Purpose of the Study:

• To introduce the mrgsolve R package for simulating ordinary differential equation-based models.
• To provide a tutorial on using mrgsolve for PBPK and QSP modeling workflows.
• To demonstrate the application of mrgsolve with real-world examples and model validation.

Main Methods:

• mrgsolve combines R and C++ for efficient simulation of hierarchical models.
• The workflow includes model specification, event specification (dosing), and post-simulation analysis.
• Examples utilize a PBPK model for voriconazole and a QSP model for colorectal cancer signaling.

Main Results:

• mrgsolve facilitates efficient simulation of both simple and complex PBPK and QSP models.
• Model validation against adult and pediatric voriconazole data was performed.
• Population simulations of combination therapies for colorectal cancer were illustrated.

Conclusions:

• mrgsolve is a versatile and efficient tool for PBPK and QSP modeling within the R ecosystem.
• The package supports a comprehensive workflow from model definition to simulation and analysis.
• Demonstrated applications highlight its utility in drug development and systems biology research.