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Pharmacodynamic modeling and optimal drug regimen for antiplatelet therapy


A. Caruso, G. Sveticic, G. Scharbert, S. Kozek-Langenecker, M. Curatolo, M. Morari

ISAP Annual Meeting, New Orleans, LA

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. Adenosine diphosphate (ADP), released by activated platelets, is a potent platelet aggregator that activates platelets by interacting with the two receptors P2Y1 and P2Y12. Methyl-S-adenosine monophosphate (MeSAMP) is a direct-acting, reversible and short-acting inhibitor of platelet P2Y12 receptor, preventing ADP-induced platelet activation and subsequent aggregation. Ilomedine, a chemically stable compound with prostacyclin PGI2 mimetic activity, inhibits platelet aggregation by stimulating adenylyl cyclase. Anti-P2Y12 drugs, by rescuing adenylyl cyclase activity, potentiate the antiplatelet effect of PGI2, which may contribute to their antithrombotic effect. To the best of our knowledge, quantitation of MeSAMP and Ilomedine antiplatelet effects has not been undertaken. The present study has multiple objectives: i) to investigate the concentration-effect relationship of the two drugs; ii) to determine the type (additivity, synergism, or antagonism) and magnitude of MeSAMP-Ilomedine pharmacodynamic interaction; iii) to find the optimal MeSAMP-Ilomedine combination in vitro, being defined as the one producing a desired anti-coagulation effect (e.g. inhibiting ADP activation below 10% of baseline) without lowering the thrombin receptor activating peptide-6 (TRAP-6) activation under normal range.


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% Autogenerated BibTeX entry
@InProceedings { CarEtal:2009:IFA_3376,
    author={A. Caruso and G. Sveticic and G. Scharbert and S. Kozek-Langenecker and M. Curatolo and M. Morari},
    title={{Pharmacodynamic modeling and optimal drug regimen for
	  antiplatelet therapy}},
    booktitle={ISAP Annual Meeting},
    address={New Orleans, LA},
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