Scale reduction of a systems coagulation model with an application to modeling pharmacokinetic-pharmacodynamic data.
CPT Pharmacometrics Syst Pharmacol
; 3: e90, 2014 Jan 08.
Article
in En
| MEDLINE
| ID: mdl-24402117
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
CPT Pharmacometrics Syst Pharmacol
Year:
2014
Document type:
Article
Affiliation country:
Nueva Zelanda