Pharmacokinetics and Pharmacodynamics of an Oral Formulation of Apixaban in Horses After Oral and Intravenous Administration.
Authors: Serpa Priscila B S, Brooks Marjory B, Divers Thomas, Ness Sally, Birschmann Ingvild, Papich Mark G, Stokol Tracy
Journal: Frontiers in veterinary science
Summary
Anticoagulation in horses typically relies on injectable heparin to manage thrombotic complications associated with inflammatory and infectious disease, creating practical challenges around daily dosing and cost. Researchers investigated apixaban, a Factor Xa inhibitor successfully used in human thromboprophylaxis, to determine whether this oral direct anticoagulant could offer horses a viable injectable-free alternative. Five horses received single doses of apixaban (0.2 mg/kg) via intravenous and oral routes in a blinded, placebo-controlled cross-over design, with plasma concentrations and anticoagulant activity measured using ultra-performance liquid chromatography-mass spectrometry and anti-Xa bioassays, whilst pharmacodynamic response was assessed via dilute prothrombin time and flow cytometric analysis of viral-induced platelet activation. Oral administration yielded no detectable plasma apixaban, whilst intravenous dosing produced rapid absorption (peak at 3 minutes) with a short half-life of 1.3 hours and high protein binding (92–99%), and notably, the drug showed no relationship to coagulation parameters and failed to inhibit herpesvirus-induced platelet activation. Although the anti-Xa assay correlated excellently with drug concentrations, the complete lack of oral bioavailability means apixaban cannot currently be recommended as an anticoagulant option for equine practice, suggesting that horses may require formulation strategies or alternative DOAC compounds to achieve therapeutic benefit from this drug class.
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Practical Takeaways
- •Apixaban has no practical clinical value for anticoagulation in horses due to complete lack of oral absorption—oral dosing would be ineffective.
- •If IV apixaban were considered, its very short half-life (1.3 hours) would require frequent dosing to maintain therapeutic levels, making it impractical compared to standard heparin protocols.
- •This study demonstrates the importance of species-specific pharmacokinetic testing before assuming human anticoagulant drugs will work in equine patients.
Key Findings
- •Apixaban showed no detectable plasma concentrations after oral administration in horses, indicating poor oral bioavailability.
- •After IV administration, apixaban had a short elimination half-life of 1.3 ± 0.2 hours with high protein binding (92-99%).
- •Apixaban did not inhibit EHV-1-induced platelet activation and showed no relationship between dilute prothrombin time and plasma concentrations.
- •Anti-Xa activity assay showed excellent correlation with UPLC-MS measurements (r² = 0.9997), validating the bioactivity method.