• Am. J. Vet. Res. · Aug 2015

    Pharmacokinetics and pharmacodynamics of the factor Xa inhibitor apixaban after oral and intravenous administration to cats.

    • Jennifer A Myers, Luke A Wittenburg, Christine S Olver, Caitlyn M Martinez, and Janice M Bright.
    • Am. J. Vet. Res. 2015 Aug 1; 76 (8): 732-8.

    ObjectiveTo determine pharmacokinetic and pharmacodynamic properties of the novel factor Xa inhibitor apixaban in clinically normal cats.Animals5 purpose-bred domestic shorthair cats.ProceduresA single dose of apixaban (0.2 mg/kg, PO) was administered to each cat (time 0), and blood samples were obtained at 0, 15, 30, 45, 60, 120, 240, 360, 480, and 1,440 minutes. After a 1-week washout period, another dose of apixaban (0.2 mg/kg, IV) was administered to each cat, and blood samples were obtained at 0, 5, 10, 15, 30, 45, 60, 120, 240, 360, 480, and 1,440 minutes. Apixaban concentrations in plasma were measured via liquid chromatography-tandem mass spectrometry. Pharmacodynamic effects of apixaban were determined with a commercial assay for factor × activity, which measures endogenous factor Xa activity chromogenically.ResultsFactor Xa was inhibited as a function of time after a single dose of apixaban administered orally or IV, and a direct inverse correlation with the plasma apixaban concentration was detected. Pharmacokinetic analysis revealed moderate clearance, short half-life, and high bioavailability for apixaban. A 2-compartment model was fit to the IV pharmacokinetic data; compartmental modeling could not be used to adequately describe the oral data because of substantial interindividual variability.Conclusions And Clinical RelevanceResults inticated that apixaban was an effective inhibitor of factor Xa in cats. Further studies will be needed to determine pharmacokinetics and pharmacodynamics after multidose administration, effects of cardiac disease on pharmacokinetics and pharmacodynamics, dosing recommendations, and efficacy of apixaban for use in the treatment and prevention of thromboembolic disease in cats.

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