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Pharmacodynamic interaction modeling and personalized drug dosing for antiplatelet therapy

Author(s):

A. Caruso, G. Sveticic, G. Scharbert, S. Kozek-Langenecker, M. Curatolo, M. Morari
Conference/Journal:

AMA-IEEE Medical Technology Conference on Individualized Healthcare, Washington, DC
Abstract:

Platelet activation and aggregation play a pivotal role in cardiovascular disease, triggering adverse events such as acute coronary syndrome and stroke. Inhibition of platelet aggregation is therefore a primary therapeutic goal. The present “one-size-fits-all” antiplatelet strategy is flawed. At one end of the spectrum, selected patients with excessively low platelet reactivity may bleed. Patients with high platelet reactivity may on the other hand be subject to ischemic events. Optimal antiplatelet therapy should entail personalizing drug dosage based on an objective assessment of the individual thrombotic potential through measurement of platelet function. ADP, a potent platelet aggregator, interacts with platelet receptors P2Y1 and P2Y12. MeSAMP prevents ADPinduced activation through P2Y12 inhibition. Prostacyclin-mimetic Iloprost inhibits aggregation by stimulating adenylyl cyclase. Quantitation of MeSAMP and iloprost antiplatelet effects has not yet been undertaken. This study has multiple objectives: i) to investigate the concentration-effect relationship of these drugs; ii) to determine the nature (additivity, synergism, or antagonism) of MeSAMP-iloprost pharmacodynamic (PD) interaction; iii) to find the optimal combination in the individual by taking into account both desired and adverse drug effects (platelet response to ADP and TRAP, respectively).

Year:

2010
Type of Publication:

(01)Article
Supervisor:



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% Autogenerated BibTeX entry
@InProceedings { CarEtal:2010:IFA_3552,
    author={A. Caruso and G. Sveticic and G. Scharbert and S. Kozek-Langenecker and M. Curatolo and M. Morari},
    title={{Pharmacodynamic interaction modeling and personalized drug
	  dosing for antiplatelet therapy}},
    booktitle={AMA-IEEE Medical Technology Conference on Individualized
	  Healthcare},
    pages={},
    year={2010},
    address={Washington, DC},
    month=mar,
    url={http://control.ee.ethz.ch/index.cgi?page=publications;action=details;id=3552}
}
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