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

Abstract

mrgsolve is an open-source R package available on the Comprehensive R Archive Network. It combines R and C++ coding for simulation from hierarchical, ordinary differential equation–based models. Its efficient simulation engine and integration into a parallelizable, R-based workflow makes mrgsolve a convenient tool both for simple and complex models and thus is ideal for physiologically-based pharmacokinetic (PBPK) and quantitative systems pharmacology (QSP) model. This tutorial will first introduce the basics of the mrgsolve simulation workflow, including model specification, the introduction of interventions (dosing events) into the simulation, and simulated results postprocessing. An applied simulation example is then presented using a PBPK model for voriconazole, including a model validation step against adult and pediatric data sets. A final simulation example is then presented using a previously published QSP model for mitogen-activated protein kinase signaling in colorectal cancer, illustrating population simulation of different combination therapies.