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Journal of veterinary pharmacology and therapeutics2021; 44(5); 724-732; doi: 10.1111/jvp.12979

Pharmacokinetics and pharmacodynamics of intravenous and oral apixaban in horses.

Abstract: Large vessel and microvascular thrombi are common complications in systemically ill horses contributing to patient morbidity and mortality. Apixaban, an oral factor Xa inhibitor, shows excellent efficacy against stroke and deep vein thrombosis in humans. The purpose of this study was to determine serum apixaban concentrations and anti-factor Xa activity in horses after orally administered apixaban. Five horses received a single dose of intravenous (0.09 mg/kg) and oral (1 mg/kg) apixaban in a cross-over design. Serum apixaban concentrations and anti-Xa activity were measured serially via liquid chromatography-tandem mass spectrometry and a commercial assay, respectively, for 12 hr following oral administration. Apixaban was detected in all horses after both oral and intravenous administration. Oral administration yielded a mean maximum concentration of 60.3 ng/ml (59.4-111 ng/ml), mean time to maximum concentration of 0.5 hr (0.5-2), mean half-life of 6.2 hr (4.6-8.3), and mean oral bioavailability of 10% (3.8-17.4). After oral administration, anti-Xa activity had a strong positive relationship with serum apixaban and was best represented by a dose-response model with the following parameters: E  = 5.00 ng/ml, E  = 311 ng/mL, EC  = 267 ng/ml, and n = 1.58. Anti-Xa activity was significantly higher 2 hr post-administration compared with baseline (p = .032). Despite low oral bioavailability, administration of 1 mg/kg oral apixaban, in healthy horses, achieves serum concentrations similar to those reported in humans. Apixaban has potential clinical utility in horses and warrants further investigation.
© 2021 John Wiley & Sons Ltd.
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Publication Date: 2021-05-27 PubMed ID: 34046920DOI: 10.1111/jvp.12979Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research study investigates the effect of apixaban, a blood thinner, on horses. It looks at how the drug’s concentration changes in horse serum when given orally and intravenously and how it impacts anti-factor Xa activity, which could help manage blood clots in horses.

Research Study Methodology and Findings

  • The study was conducted on five horses that were given a single dose of intravenous (0.09 mg/kg) and oral (1 mg/kg) apixaban. The drug regimen was designed as a cross-over trial where each horse experienced both forms of administration but at different times.
  • To measure the concentration of apixaban in the blood serum, the researchers used liquid chromatography-tandem mass spectrometry, a biochemical technique known for its sensitivity and accuracy. The detection of anti-factor Xa activity, which indicates inhibition of clot-promoting proteins, was carried out using a commercial assay. These measurements were done for 12 hours following the oral administration of apixaban.
  • The researchers found that apixaban was detected in all the horses regardless of the administration method. However, the oral administration resulted in a lower bioavailability of the drug. Bioavailability refers to the proportion of a drug or other substance that enters circulation when introduced into the body and so is able to have an active effect.
  • Following oral administration, the average highest concentration was 60.3 ng/ml, the average time to the highest concentration was 0.5 hours, the average half-life for the drug was 6.2 hours, and the average oral bioavailability was 10%.
  • The anti-factor Xa activity in the horses showed a strong positive correlation with serum apixaban. This means that as the amount of apixaban in the blood increased, so did the anti-factor Xa activity. The researchers were able to model this relationship using a dose-response model.
  • Two hours after administration, anti-Xa activity was significantly higher compared to baseline levels, suggesting that the drug was functionally active.

Implications of the Findings

  • Despite the low oral bioavailability, the concentration of apixaban achieved in horse serum following oral administration was within the range reported in human studies. This suggests a potential for apixaban to be used effectively in horses.
  • The study provides promising preliminary results for the use of apixaban in preventing and treating deep vein thrombosis and stroke in horses. However, further research is needed to assess the drug’s safety, efficacy, and optimal dosing in horses.

Cite This Article

APA
Wallace GE, McKaba VF, Reinhart JM, Li Z, Austin S, Fries RC. (2021). Pharmacokinetics and pharmacodynamics of intravenous and oral apixaban in horses. J Vet Pharmacol Ther, 44(5), 724-732. https://doi.org/10.1111/jvp.12979

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 44
Issue: 5
Pages: 724-732

Researcher Affiliations

Wallace, Gabrielle E
  • University of Illinois at Urbana-Champaign, College of Veterinary Medicine, Urbana, IL, USA.
McKaba, Victoria F
  • University of Illinois at Urbana-Champaign, College of Veterinary Medicine, Urbana, IL, USA.
Reinhart, Jennifer M
  • University of Illinois at Urbana-Champaign, College of Veterinary Medicine, Urbana, IL, USA.
Li, Zhong
  • The Metabolomics Center Roy J Carver Biotechnology Center, University of Illinois at Urbana Illinois, Urbana, IL, USA.
Austin, Scott
  • University of Illinois at Urbana-Champaign, College of Veterinary Medicine, Urbana, IL, USA.
Fries, Ryan C
  • University of Illinois at Urbana-Champaign, College of Veterinary Medicine, Urbana, IL, USA.

MeSH Terms

  • Administration, Intravenous / veterinary
  • Administration, Oral
  • Animals
  • Factor Xa Inhibitors
  • Horses
  • Humans
  • Pyrazoles / pharmacology
  • Pyridones / pharmacology

Grant Funding

  • United States Department of Agriculture

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