This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The purpose of these studies was to define the antithrombotic effects and bleeding potential of small molecule inhibitor of factor VIIa (FVIIa), in a baboon model of arterial thrombosis. FVIIa inhibitors have been evaluated in a variety of in-vitro assays and in pharmacokinetic studies. Potency has been determined using enzyme inhibition assays and by determining the plasma concentration of inhibitor required to prolong the prothrombin time (PT). Selectivity has been determined by comparing the potency of inhibitors in the factor VIIa enzyme assay to their potency in assays for other serine proteases of the coagulation and fibrinolytic systems, and by comparing the concentrations required to increase the activated partial thromboplastin time (APTT). PT and APTT assays performed using plasmas from a variety of species have shown that these inhibitors may lose potency and selectivity in non-primate species, but may retain their potency and selectivity in primates.
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