Key result
In healthy cats, a single dose of apixaban effectively inhibited factor Xa, with activity significantly inversely correlated with plasma apixaban concentration after IV and oral administration.
Why the study?
What are the pharmacokinetic and pharmacodynamic properties of apixaban after oral and intravenous administration in clinically normal cats?
What are the pharmacokinetic and pharmacodynamic properties of apixaban after oral and intravenous administration in clinically normal cats?
Effect estimate: R = -0.944 (IV) and R = -0.548 (PO)
p-value: p=<0.001
Apixaban demonstrates effective factor Xa inhibition with high bioavailability in clinically normal cats, supporting further investigation for veterinary thromboembolic disease.
Establishes apixaban pharmacokinetics in cats; leaves open clinical dosing and efficacy in feline thromboembolism.
OBJECTIVE: To determine pharmacokinetic and pharmacodynamic properties of the novel factor Xa inhibitor apixaban in clinically normal cats. ANIMALS: 5 purpose-bred domestic shorthair cats. PROCEDURES: A 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. RESULTS: Factor 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 RELEVANCE: Results 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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Myers et al. (2015) studied Healthy (n=5). Apixaban vs. Self (crossover) was evaluated on Factor Xa activity correlation with plasma apixaban concentration (R = -0.944 (IV) and R = -0.548 (PO), p=<0.001). In healthy cats, a single dose of apixaban effectively inhibited factor Xa, with activity significantly inversely correlated with plasma apixaban concentration after IV and oral administration.
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