Peer-reviewed veterinary case report
How apixaban works and lasts in healthy dogs
By Herrera, Noelle D et al.·Published in Frontiers in veterinary science·2021·Department of Clinical Sciences, United States·View original on PubMed →
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Original publication title: Pharmacokinetics and Biologic Activity of Apixaban in Healthy Dogs.
- Species:
- dog
Plain-English summary
A group of six healthy mixed-breed dogs were given a medication called apixaban to see how well it works and how the body processes it. They received the drug both through an injection and orally. The dogs tolerated both forms of the medication well, and the injection was found to significantly affect their blood clotting times for up to an hour. The oral version also had an effect, but it was less consistent. This study helps understand how apixaban could be used for dogs that may need treatment for blood clotting issues in the future.
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Abstract
Thrombosis is common in critically ill dogs and causes considerable morbidity and mortality. The direct factor Xa inhibitor apixaban is safe, efficacious, and convenient in humans. This study aimed to determine the pharmacokinetics (PK), bioactivity, protein binding, and bioavailability of apixaban following intravenous (IV) and oral (PO) administration to healthy dogs. Six healthy, adult, mixed-breed dogs were administered apixaban 0.18 mg/kg IV and then following a minimum 2-week washout period administered apixaban 0.2 mg/kg PO. Dogs were monitored using an apixaban-calibrated anti-Xa bioassay, prothrombin time (PT) and activated partial thromboplastin time (aPTT) and tissue-factor thromboelastography (TF-TEG). Plasma apixaban concentrations were measured using liquid chromatography-tandem mass spectrometry. Concentration-time plots were constructed, and PK modeling performed using compartmental methods. Administration of IV and PO apixaban was well-tolerated. Following IV administration, mean half-life was 4.1 h, and volume of distribution was 177 ml/kg. Apixaban was highly protein bound (98.6%). Apixaban concentrations and anti-Xa activity were highly correlated (R0.994,< 0.0001). Intravenous apixaban significantly prolonged PT at time points up to 1 h, and aPTT at time points up to 0.25 h post-administration. Coagulation times were positively correlated with apixaban concentrations (PT R0.599,< 0.0001; aPTT R0.430,< 0.0001) and TF-TEG R-time was significantly prolonged 0.25 h post-administration. Following oral administration, mean bioavailability was 28.4%, lag time was 2 h, time to Cwas 5 h and the apparent elimination half-life was 3.1 h. Oral apixaban significantly prolonged PT at 4, 6, and 8 h but aPTT and TF-TEG were not consistently affected by oral apixaban. Apixaban concentrations are best monitored using anti-Xa activity. Future studies should determine PK and bioactivity of other doses using commercial tablets and following multidose administration and establish safe, effective dosing ranges in sick dogs.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/34291105/