This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. These ongoing studies will demonstrate dose responsive efficacy of a novel orally available coagulation factor Xa inhibitor, PRT054021, in the Hanson baboon thrombosis model. The efficacy seen with PRT054021 will be compared to the the level of efficacy with two other antithrombotic compounds in this thrombosis model. One of these, Arixtra, is an approved pentasaccharide indirect FXa inhibitor for prevention of thrombosis after knee or hip joint replacement, but its mechanism of action is still ATIII dependent. The other compound, PRT584247 is a direct FXa inhibitor that has shown efficacy at preventing thrombosis in Phase II human clinical trials in patients undergoing knee replacement. The experimental baboon results will be bridged (via the in vivo concentration to antithrombotic effect relationship) for all three compounds in an effort to estimate the expected human therapeutic dose of PRT054021 in humans who are at risk for venous thrombosis (patients undergoing knee or hip joint replacement).
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