Burghaus2011 - Simulating Rivaroxaban effects on blood coagulation
Model Identifier
MODEL1805140001
Short description
Another mathematical model of blood coagulation.
Format
SBML
(L2V4)
Related Publication
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Evaluation of the efficacy and safety of rivaroxaban using a computer model for blood coagulation.
- Burghaus R, Coboeken K, Gaub T, Kuepfer L, Sensse A, Siegmund HU, Weiss W, Mueck W, Lippert J
- PloS one , 4/ 2011 , Volume 6 , Issue 4 , pages: e17626 , PubMed ID: 21526168
- Bayer Schering Pharma AG, Wuppertal, Germany. Bayer Technology Services GmbH, Leverkusen, Germany. Bayer Schering Pharma AG, Berlin, Germany.
- Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.
Contributors
Submitter of the first revision: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts
Metadata information
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Curation status
Non-curated
Tags
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
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Model files |
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| Burghaus2011.xml | SBML L2V4 representation of Burghaus2011 - Simulating Rivaroxaban effects on blood coagulation | 594.10 KB | Preview | Download |
Additional files |
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| Burghaus2011.cps | Curated and annotated model COPASI file. Curated figure could be improved. Prothrombin time (Fibrin) is a bit soon (10 instead of 12 seconds) and time to plateau is a bit soon (20 instead of 20 seconds). Thrombin is also slightly underestimated. | 734.72 KB | Preview | Download |
| figure4.png | Attempt at reproducing figure 4. | 16.50 KB | Preview | Download |
- Model originally submitted by : Matthew Roberts
- Submitted: May 21, 2018 4:07:52 PM
- Last Modified: May 21, 2018 4:07:52 PM
Revisions
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Version: 3
- Submitted on: May 21, 2018 4:07:52 PM
- Submitted by: Matthew Roberts
- With comment: Uploaded curation figure.