Model reduction in mathematical pharmacology : Integration, reduction and linking of PBPK and systems biology models.

ABSTRACT: In this paper we present a framework for the reduction and linking of physiologically based pharmacokinetic (PBPK) models with models of systems biology to describe the effects of drug administration across multiple scales. To address the issue of model complexity, we propose the reduction of each type of model separately prior to being linked. We highlight the use of balanced truncation in reducing the linear components of PBPK models, whilst proper lumping is shown to be efficient in reducing typically nonlinear systems biology type models. The overall methodology is demonstrated via two example systems; a model of bacterial chemotactic signalling in Escherichia coli and a model of extracellular regulatory kinase activation mediated via the extracellular growth factor and nerve growth fa

SUBMITTER: Snowden TJ 

PROVIDER: S-EPMC6061126 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature