Demin2013 - PKPD behaviour - 5-Lipoxygenase inhibitors

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Model Identifier
BIOMD0000000490
Short description
Demin2013 - PKPD behaviour - 5-Lipoxygenase inhibitors

This model is described in the article:

Systems pharmacology models can be used to understand complex pharmacokinetic-pharmacodynamic behavior: an example using 5-lipoxygenase inhibitors.
Demin O, Karelina T, Svetlichniy D, Metelkin E, Speshilov G, Demin O Jr, Fairman D, van der Graaf PH, Agoram BM.
CPT Pharmacometrics Syst Pharmacol 2013; 2: e74

Abstract:

Zileuton, a 5-lipoxygenase (5LO) inhibitor, displays complex pharmaokinetic (PK)-pharmacodynamic (PD) behavior. Available clinical data indicate a lack of dose-bronchodilatory response during initial treatment, with a dose response developing after ~1-2 weeks. We developed a quantitative systems pharmacology (QSP) model to understand the mechanism behind this phenomenon. The model described the release, maturation, and trafficking of eosinophils into the airways, leukotriene synthesis by the 5LO enzyme, leukotriene signaling and bronchodilation, and the PK of zileuton. The model provided a plausible explanation for the two-phase bronchodilatory effect of zileuton-the short-term bronchodilation was due to leukotriene inhibition and the long-term bronchodilation was due to inflammatory cell infiltration blockade. The model also indicated that the theoretical maximum bronchodilation of both 5LO inhibition and leukotriene receptor blockade is likely similar. QSP modeling provided interesting insights into the effects of leukotriene modulation.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e74; doi:10.1038/psp.2013.49; advance online publication 11 September 2013.

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Format
SBML (L2V4)
Related Publication
  • Systems pharmacology models can be used to understand complex pharmacokinetic-pharmacodynamic behavior: an example using 5-lipoxygenase inhibitors.
  • O Demin, T Karelina, D Svetlichniy, E Metelkin, G Speshilov, O Demin, D Fairman, P H van der Graaf, B M Agoram
  • CPT: pharmacometrics & systems pharmacology , 9/ 2013 , Volume 2 , pages: e74 , PubMed ID: 24026253
Contributors
Submitter of the first revision: Vijayalakshmi Chelliah
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modellers: administrator, Vijayalakshmi Chelliah

Metadata information

is (2 statements)
BioModels Database BIOMD0000000490
BioModels Database MODEL1309160000

isDescribedBy (1 statement)
PubMed 24026253

isDerivedFrom (3 statements)
PubMed 21560018
PubMed 22020181
PubMed 23146124

hasTaxon (1 statement)
Taxonomy Homo sapiens

isVersionOf (2 statements)
hasVersion (1 statement)
Human Disease Ontology asthma

hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated
Modelling approach(es)
ordinary differential equation model

Connected external resources