The Direct Factor Xa Inhibitor Apixaban Produces Broad Antithrombotic Activity with Limited Effects on Bleeding Time in Rats
| Autor: | William A. Schumacher, Pancras C. Wong, Jeffrey S. Bostwick, Anne B. Stewart, Thomas E. Steinbacher, Donald J. P. Pinto |
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| Rok vydání: | 2007 |
| Předmět: |
Prothrombin time
medicine.medical_specialty medicine.diagnostic_test medicine.drug_mechanism_of_action business.industry Immunology Factor Xa Inhibitor Urology Cell Biology Hematology Biochemistry Tissue factor Bleeding time Hemostasis Antithrombotic Medicine Apixaban business Fibrinolytic agent medicine.drug |
| Zdroj: | Blood. 110:4005-4005 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Apixaban is an oral, direct and highly selective factor Xa inhibitor which is in late stage clinical development for the prevention and treatment of thromboembolic diseases. Apixaban is potent against human and rat factor Xa (Ki = 0.08 and 1.3 nM, respectively). The efficacy/safety profile of apixaban was determined in experimental models of thrombosis and hemostasis performed in anesthetized rats. Thrombosis was induced either by topical application of FeCl2 to the vena cava (VT) or carotid artery (AT), tissue factor infusion into the vena cava (TF-VT), or within an extracorporeal arterial-venous shunt (ST). Bleeding time was measured in response to template incision of the renal cortex. Apixaban was administered as a continuous i.v. infusion of 0.1, 0.3, 1 or 3 mg/kg/h starting 60 min before each experimental procedure (n=5 or 6 per dose). These respective doses increased the ex vivo prothrombin time by 1.3, 1.9, 3.0 and 3.9 times control baseline, and achieved plasma concentrations of 0.3, 1.4, 5.0 and 12.2 μM. In comparison to vehicle treatment, the 3 mg/kg/h dose of apixaban decreased thrombus weight by 90 ± 2% in VT, 62 ± 7% in TF-VT, 62 ± 4% in AT, and 79 ± 3% in ST (all p |
| Databáze: | OpenAIRE |
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