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Home / Equine Research Bank / Front Vet Sci / Pharmacokinetics and Pharmacodynamics of an Oral Formulation...
Frontiers in veterinary science2018; 5; 304; doi: 10.3389/fvets.2018.00304

Pharmacokinetics and Pharmacodynamics of an Oral Formulation of Apixaban in Horses After Oral and Intravenous Administration.

Abstract: Horses with inflammatory and infectious disorders are often treated with injectable heparin anticoagulants to prevent thrombotic complications. In humans, a new class of direct oral acting anticoagulants (DOAC) appear as effective as heparin, while eliminating the need for daily injections. Our study in horses evaluated apixaban, a newly approved DOAC for human thromboprophylaxis targeting activated factor X (Xa). Our goals were to: (1) Determine pharmacokinetics and pharmacodynamics of apixaban after oral (PO) and intravenous (IV) administration in horses; (2) Detect any inhibitory effects of apixaban on Equid herpesvirus type 1 (EHV-1)-induced platelet activation, and (3) Compare an anti-Xa bioactivity assay with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) for measuring apixaban concentrations. In a blinded placebo-controlled cross-over study, five horses received a single dose (0.2 mg/kg) of apixaban or placebo PO or IV. Blood was collected before and at 3 (IV) or 15 (PO) min, 30 and 45 min, and 1, 2, 3, 4, 6, 8, and 24 h after dosing for measuring apixaban UPLC-MS concentrations and anti-Xa activity. Pharmacodynamic response was measured in a dilute prothrombin time (dPT) assay. Flow cytometric EHV-1-induced platelet P-selectin expression and clinical pathologic safety testing were performed at baseline, 2 and 24 h and baseline and 24 h, respectively. We found no detectable apixaban in plasma PO administration. After IV administration, plasma apixaban levels followed a two-compartment model, with concentrations peaking at 3 min and decreasing to undetectable levels by 8 h. The elimination half-life was 1.3 ± 0.2 h, with high protein binding (92-99%). The dPT showed no relationship to apixaban UPLC-MS concentration and apixaban did not inhibit EHV-1-induced platelet activation after IV dosing. Apixaban anti-Xa activity showed excellent correlation to UPLC-MS ( = 0.9997). Our results demonstrate that apixaban has no apparent clinical utility as an anticoagulant for horses due to poor oral availability.
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Publication Date: 2018-12-04 PubMed ID: 30564584PubMed Central: PMC6288471DOI: 10.3389/fvets.2018.00304Google 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 article discusses the pharmacokinetics and pharmacodynamics study of the drug Apixaban in horses, administered both orally and intravenously. The study indicates that Apixaban, a common anticoagulant for humans, was ineffective in horses due to poor oral absorption.

Study Overview

The study aimed to understand the effects and potential clinical use of oral anticoagulants on horses. Horses suffering from inflammatory and infectious diseases often need to be treated with injectable anticoagulants like heparin to avoid clot-related complications. The researchers evaluated Apixaban, a new class of anticoagulant termed Direct Oral Acting Anticoagulant (DOAC), as a potential alternative.

Research Objectives

The study set out to meet three key objectives:

  • Assess the pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body) of Apixaban when administered orally or through IV in horses.
  • Identify any inhibitory effects of Apixaban on Equid herpesvirus type 1 (EHV-1)-induced platelet activation.
  • Compare an anti-Xa bioactivity assay with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to measure Apixaban’s concentrations.

Methodology

In a blinded, placebo-controlled crossover study, the researchers administered Apixaban or a placebo to five horses either orally or intravenously at a dose of 0.2mg/kg. Blood samples were collected before administering and at multiple points post-dosing. The researchers measured Apixaban concentrations with a UPLC-MS. Pharmacodynamic responses were analyzed using a dilute prothrombin time (dPT) assay.

Results

After oral administration, Apixaban was not detected in horse plasma, indicating poor oral absorption. Post-IV administration, Apixaban concentrations peaked at 3 minutes and became undetectable by the 8th hour. The elimination half-life was approximately 1.3 hours with high protein binding of 92-99%. The dPT showed no correlation to Apixaban concentrations, and Apixaban did not inhibit EHV-1-induced platelet activation, as measured with flow cytometry. However, the test for anti-Xa activity displayed a strong correlation ( = 0.9997) with UPLC-MS results.

Conclusion

Based on the results, Apixaban’s usage as an anticoagulant for horses appears limited due to its poor oral availability. It did not inhibit EHV-1-induced platelet activation and showed no correlation with the dPT. The research contributes to the body of knowledge on medication for horses and proves valuable for future studies on anticoagulants for veterinary use.

Cite This Article

APA
Serpa PBS, Brooks MB, Divers T, Ness S, Birschmann I, Papich MG, Stokol T. (2018). Pharmacokinetics and Pharmacodynamics of an Oral Formulation of Apixaban in Horses After Oral and Intravenous Administration. Front Vet Sci, 5, 304. https://doi.org/10.3389/fvets.2018.00304

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 5
Pages: 304
PII: 304

Researcher Affiliations

Serpa, Priscila B S
  • Department of Population Medicine and Diagnostic Science, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Brooks, Marjory B
  • Department of Population Medicine and Diagnostic Science, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Divers, Thomas
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Ness, Sally
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Birschmann, Ingvild
  • Institut für Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
Papich, Mark G
  • Department of Molecular Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Stokol, Tracy
  • Department of Population Medicine and Diagnostic Science, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.

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Citations

This article has been cited 3 times.
  1. Herrera ND, Birschmann I, Wolny M, Papich MG, Brooks MB, Goggs R. Pharmacokinetics and Biologic Activity of Apixaban in Healthy Dogs. Front Vet Sci 2021;8:702821.
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  2. Rosa B. Equine Drug Transporters: A Mini-Review and Veterinary Perspective. Pharmaceutics 2020 Nov 8;12(11).
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  3. Miglio A, Falcinelli E, Mezzasoma AM, Busechian S, Rueca F, Gresele P, Antognoni MT. Biomarkers of in vivo platelet activation in thoroughbreds during their first long-term training. Front Vet Sci 2024;11:1395423.
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