Comparison of the Pharmacokinetics and Pharmacodynamics of Apixaban and Rivaroxaban in Dogs

Overview

Journal J Vet Intern Med

Specialties General Medicine
Veterinary Medicine

Date 2024 Oct 17

PMID 39417527

Authors

Alex M Lynch

Laura K Ruterbories

Yao Zhu

Frank Fialkiewicz

Mark G Papich

Marjory B Brooks

Robert Goggs

Affiliations

Soon will be listed here.

Abstract

Background: Comparative pharmacokinetics and pharmacodynamics (PK/PD) of apixaban and rivaroxaban have not been studied in dogs and the propensity of these drugs to cause hypercoagulability after discontinuation is unknown.

Hypothesis: Compare the PK/PD of clinical dosing regimens of PO apixaban and rivaroxaban administered repeatedly to healthy dogs and assess the effect of abrupt drug discontinuation on coagulation.

Animals: Six University-owned, purpose-bred, middle-aged, mixed-breed dogs (4 male, 2 female).

Methods: Dogs were given apixaban or rivaroxaban PO at 0.5 mg/kg q12h for 7 days with a 14-day washout period between drugs. Plasma drug concentrations were quantitated, and anticoagulant effects were measured using clotting times, calibrated anti-Xa bioactivity assays, and measurements of thrombin generation. The potential for rebound hypercoagulability was assessed by measuring D-dimers, thrombin-antithrombin (TAT) complexes, and antithrombin activity after drug discontinuation.

Results: Plasma drug concentrations and anti-Xa bioactivities were closely correlated for both drugs, but drug concentrations varied considerably among dogs, despite consistent dose regimens. Thrombin generation variables were significantly correlated with the anti-Xa bioactivity of both drugs and no significant differences in the effects of apixaban and rivaroxaban on thrombin generation were observed. Drug discontinuation had no effect on D-dimer concentrations. The concentration of TAT complexes decreased after apixaban discontinuation and did not change after rivaroxaban discontinuation.

Conclusions And Clinical Importance: Repeated PO administration of apixaban or rivaroxaban to healthy dogs produced comparable anticoagulant effects measured by inhibition of thrombin formation. Rebound hypercoagulability after drug discontinuation was not observed and weaning of these drugs in clinical patients might not be necessary.

Citing Articles

Comparison of the pharmacokinetics and pharmacodynamics of apixaban and rivaroxaban in dogs.

Lynch A, Ruterbories L, Zhu Y, Fialkiewicz F, Papich M, Brooks M J Vet Intern Med. 2024; 38(6):3242-3254.

PMID: 39417527 PMC: 11586571. DOI: 10.1111/jvim.17216.

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