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


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


METHODS
Veterinary university teaching hospital.


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


METHODS
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.


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.
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602.
Amy C
AC
Dixon-Jimenez
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602. brainard@uga.edu.
Benjamin M
BM
Brainard
the Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14850.
Marjory B
MB
Brooks
Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849.
Ben
B
Nie
Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849.
Robert D
RD
Arnold
Pharmaceutical Specialties, Inc, Bogart, GA, 30622.
Daniel
D
Loper
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602.
Jessica C
JC
Abrams
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602.
Gregg S
GS
Rapoport
D000284:Administration, Oral; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests / Q000662:veterinary; D002415:Cats / Q000378:metabolism*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D008297:Male; D010314:Partial Thromboplastin Time; D011446:Prospective Studies; D011517:Prothrombin Time; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban
anticoagulant therapy; feline; hemostasis; oral FXa inhibitor