- Title
- Scale reduction of a systems coagulation model with an application to modeling pharmacokinetic-pharmacodynamic data.
- Creator
- Gulati, A.; Isbister, G. K.; Duffull, S. B.
- Relation
- CPT: Pharmacometrics Systems Pharmacology Vol. 3
- Publisher Link
- http://dx.doi.org/10.1038/psp.2013.67
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2014
- Description
- 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.
- Subject
- snakebite; evenoming; pharmacology; coagulation
- Identifier
- http://hdl.handle.net/1959.13/1045912
- Identifier
- uon:14545
- Identifier
- ISSN:2163-8306
- Language
- eng
- Full Text
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