Pharmacokinetics of Apixaban in Dogs
Fellow: Noelle Herrera
Mentor: Robert Goggs
Co-Mentor: Marjory Brooks
DESCRIPTION (provided by applicant):
Thrombosis is commonly encountered in critically ill dogs and causes considerable morbidity and mortality. In spite of this high incidence of thrombotic complications, veterinary clinicians currently have few anticoagulants with proven safety or efficacy to prevent thrombus formation or treat existing thrombi. Apixaban is a direct Factor X inhibitor, representative of a new class of anticoagulant drugs that has revolutionized the treatment and prevention of thrombosis in people. The pharmacokinetics (PK) of apixaban are established in cats and in horses, but there is very limited data on apixaban in dogs. The objective of this proposal is to determine the PK properties of apixaban following intravenous and oral administration to healthy dogs, to determine the degree of protein binding and measure oral bioavailability of the drug. We hypothesize that in dogs, apixaban has reproducible pharmacokinetics following intravenous and oral administration and has good oral bioavailability. We will evaluate the PK of apixaban following intravenous and oral administration of apixaban to 6 healthy, middle-aged mixed-breed dogs. This population models the signalment of target patient populations. Apixaban concentrations will be measured using a previously validated HPLC-MS/MS assay and the PK parameters modeled using standard software. Protein binding will be measured by ultrafiltration and oral bioavailability calculated from PK data derived from IV and PO administration.