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Updated: May 4, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Scale reduction of a systems coagulation model with an application to modeling pharmacokinetic-pharmacodynamic data
A Gulati1, G K Isbister2, S B Duffull1
1School of Pharmacy, University of Otago, Dunedin, New Zealand.
Abstract:
Bridging systems biology and pharmacokinetics-pharmacodynamics has resulted in models that are highly complex and complicated. They usually contain large numbers of states and parameters and describe multiple input-output relationships. Based on any given data set relating to a specific input-output process, it is possible that some states of the system are either less important or have no influence at all. In this study, we explore a simplification of a systems pharmacology model of the coagulation network for use in describing the time course of fibrinogen recovery after a brown snake bite. The technique of proper lumping is used to simplify the 62-state systems model to a 5-state model that describes the brown snake venom-fibrinogen relationship while maintaining an appropriate mechanistic relationship. The simplified 5-state model explains the observed decline and recovery in fibrinogen concentrations well. The techniques used in this study can be applied to other multiscale models.
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