Principal Investigator: Robert Goggs

Co-PI: Marjory Brooks

DESCRIPTION (provided by applicant): 

Thrombosis is a major, and often fatal, complication of common immune, metabolic, and inflammatory disorders in dogs. Anticoagulant therapy for dogs is now largely empiric, with little evidence to guide drug use. New orally active anticoagulant drugs (DOACs) have revolutionized thrombosis management in humans due to their ease of use and efficacy. Apixaban and rivaroxaban are the most prescribed DOACs and have a similar mechanism of action via direct inhibition of Factor Xa. Recent studies in humans suggest that apixaban has a more favorable safety profile than rivaroxaban. Although veterinarians have begun treating patients with these drugs, the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban and apixaban have not been directly compared in dogs. Moreover, the risk of recurrent thrombosis in dogs following abrupt drug cessation is unknown.

These data are required to develop clinical guidelines for dose, dosing interval and duration in dogs, and will enable design of definitive treatment trials. To fill these knowledge gaps, we will compare the PK/PD of 0.5mg/kg of apixaban (Eliquis®) and rivaroxaban (Xarelto®) administered orally, twice daily for 7 days to 6 healthy dogs. We will measure drug concentration in plasma using liquid chromatography/mass spectrometry and assess biologic effects using clotting time tests and anti-Xa assays. We will model PK and PD parameters for the two drugs and compare relative potency. Additionally, we will determine whether drug cessation without dose taper or interval extension results in rebound hypercoagulability based on a test panel measuring antithrombin, fibrinogen, D-dimers, and thrombinantithrombin complexes.