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CPT Pharmacometrics Syst Pharmacol. 2014 Jan 8;3:e90. doi: 10.1038/psp.2013.67.

Scale reduction of a systems coagulation model with an application to modeling pharmacokinetic-pharmacodynamic data.

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School of Pharmacy, University of Otago, Dunedin, New Zealand.
1] Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, New South Wales, Australia [2] Discipline of Clinical Pharmacology, University of Newcastle, New South Wales, Australia.


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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