Automated Scale Reduction of Nonlinear QSP Models With an Illustrative Application to a Bone Biology System

Integrating quantitative systems pharmacology (QSP) into pharmacokinetics/pharmacodynamics (PKPD) has resulted in models that are highly complex and often not amenable to further exploration via estimation or design. Because QSP models are usually depicted using nonlinear differential equations it i...

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Published in:CPT: pharmacometrics and systems pharmacology 2018-09, Vol.7 (9), p.562-572
Main Authors: Hasegawa, Chihiro, Duffull, Stephen B.
Format: Article
Language:English
Subjects:
Approximation
Automation
Biology
Monoclonal antibodies
Ordinary differential equations
Parameter estimation
Physiology
Studies
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description Integrating quantitative systems pharmacology (QSP) into pharmacokinetics/pharmacodynamics (PKPD) has resulted in models that are highly complex and often not amenable to further exploration via estimation or design. Because QSP models are usually depicted using nonlinear differential equations it is not straightforward to apply some model reduction techniques, such as proper lumping. In this study, we explore the combined use of linearization and proper lumping as a general method to simplification of a nonlinear QSP model. We illustrate this with a bone biology model and the reduced model was then applied to describe bone mineral density (BMD) changes due to denosumab dosing. The methodologies used in this study can be applied to other multiscale models for developing a mechanism‐based structural model for future analyses.
doi_str_mv 10.1002/psp4.12324
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subjects Approximation
Automation
Biology
Monoclonal antibodies
Ordinary differential equations
Parameter estimation
Physiology
Studies
title Automated Scale Reduction of Nonlinear QSP Models With an Illustrative Application to a Bone Biology System
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