Articles
Clinical Pharmacology & Therapeutics (2009); 86 3, 290–298. doi:10.1038/clpt.2009.87
A Comprehensive Model for the Humoral Coagulation Network in Humans
T Wajima1,2, G K Isbister3,4 and S B Duffull1
- 1School of Pharmacy, University of Otago, Dunedin, New Zealand
- 2Clinical Pharmacology and Pharmacokinetics, Shionogi, Osaka, Japan
- 3Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle Hospital, Waratah, Australia
- 4Menzies School of Health Research, Charles Darwin University, Royal Darwin Hospital, Tiwi, Australia
Correspondence: SB Duffull, (stephen.duffull@otago.ac.nz)
Received 12 February 2009; Accepted 15 April 2009; Published online 10 June 2009.
Abstract
Coagulation is an important process in hemostasis and comprises a complicated interaction of multiple enzymes and proteins. We have developed a mechanistic quantitative model of the coagulation network. The model accurately describes the time courses of coagulation factors following in vivo activation as well as in vitro blood coagulation tests of prothrombin time (PT, often reported as international normalized ratio (INR)) and activated partial thromboplastin time (aPTT). The model predicts the concentration–time and time–effect profiles of warfarin, heparins, and vitamin K in humans. The model can be applied to predict the time courses of coagulation kinetics in clinical situations (e.g., hemophilia) and for biomarker identification during drug development. The model developed in this study is the first quantitative description of the comprehensive coagulation network.
