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J Vet Emerg Crit Care (San Antonio). 2016 Sep;26(5):619-29. doi: 10.1111/vec.12524. Epub 2016 Sep 6.

Pharmacokinetic and pharmacodynamic evaluation of oral rivaroxaban in healthy adult cats.

Author information

1
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602.
2
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602. brainard@uga.edu.
3
the Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14850.
4
Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849.
5
Pharmaceutical Specialties, Inc, Bogart, GA, 30622.

Abstract

OBJECTIVES:

To determine the pharmacodynamics and pharmacokinetics of rivaroxaban (RVX), in healthy cats and to evaluate the clinicopathologic effects of various plasma RVX concentrations within target therapeutic ranges established for people.

DESIGN:

Prospective randomized cross-over study performed between July 2013 and November 2014.

SETTING:

Veterinary university teaching hospital.

ANIMALS:

Six healthy adult domestic shorthair cats (3 males, 3 females).

INTERVENTIONS:

Cats were treated with oral RVX at single, fixed doses (1.25, 2.5, 5 mg PO), q 12 h for 3 days (1.25 mg); q 24 h for 7 days (2.5 mg); and q 24 h for 28 days (1.25 mg). Blood samples were collected for complete blood count, blood chemistry, and RVX anticoagulant activity based on prolongation of dilute prothrombin time, activated partial thromboplastin time (aPTT), activated Factor X (FXa) inhibition (anti-Xa activity [aXa]) and high-pressure liquid chromatography tandem mass spectrometry determination of drug concentration.

MEASUREMENTS AND MAIN RESULTS:

Treated cats had no signs of hemorrhage or clinicopathologic off-target adverse effects. There were dose-dependent prolongations of coagulation times and increase in aXa, with peak effect at 3 hours postadministration. There was a direct correlation between plasma RVX concentration and dilute prothrombin time and aXa. Coagulation parameters returned to baseline by 24 hours after the last dose.

CONCLUSIONS:

Oral RVX was well tolerated by healthy cats with predictable pharmacokinetics and anticoagulant effects. Clinical studies of RVX are warranted in cats with heart disease.

KEYWORDS:

anticoagulant therapy; feline; hemostasis; oral FXa inhibitor

PMID:
27599304
DOI:
10.1111/vec.12524
[Indexed for MEDLINE]

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