Scale Reduction of a Systems Coagulation Model With an Application to Modeling Pharmacokinetic–Pharmacodynamic Data

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. CPT Pharmacometrics Syst. Pharmacol . (2014) 3, e90; doi: 10.1038/psp.2013.67 ; published online 8 January 2014