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Pharmacodynamic and pharmacokinetic evaluation of clopidogrel and the carboxylic acid metabolite SR 26334 in healthy dogs

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  • 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
  • | 3 Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606
  • | 4 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602

Abstract

Objective—To determine pharmacodynamic and pharmacokinetic properties of clopidogrel and the metabolite SR 26334 in dogs.

Animals—9 mixed-breed dogs.

Procedures—8 dogs received clopidogrel (mean ± SD 1.13 ± 0.17 mg/kg, PO, q 24 h) for 3 days; 5 of these dogs subsequently received a lower dose of clopidogrel (0.5 ± 0.18 mg/kg, PO, q 24 h) for 3 days. Later, 5 dogs received clopidogrel (1.09 ± 0.12 mg/kg, PO, q 24 h) for 5 days. Blood samples were collected for optical platelet aggregometry, citrated native and platelet mapping thrombelastography (TEG), and measurement of plasma drug concentrations. Impedance aggregometry was performed on samples from 3 dogs in each 3-day treatment group.

Results—ADP-induced platelet aggregation decreased (mean ± SD 93 ± 6% and 80 ± 22% of baseline values, respectively) after 72 hours in dogs in both 3-day treatment groups; duration of effect ranged from > 3 to > 7 days. Platelet mapping TEG and impedance aggregometry yielded similar results. Citrated native TEG was not different among groups. Clopidogrel was not detected in any samples; in dogs given 1.13 ± 0.17 mg/kg, maximum concentration of SR 26334 (mean ± SD, 0.206 ± 0.2 μg/mL) was detected 1 hour after administration.

Conclusions and Clinical Relevance—Clopidogrel inhibited ADP-induced platelet aggregation in healthy dogs and may be a viable antiplatelet agent for use in dogs.

Impact for Human Medicine—Pharmacodynamic effects of clopidogrel in dogs were similar to effects reported in humans; clopidogrel may be useful in studies involving dogs used to investigate human disease.

Contributor Notes

Supported by the Morris Animal Foundation (MAF D07CA-303) and the University of Georgia Clinical Research Committee.

Presented in abstract form at the American College of Veterinary Internal Medicine Forum, San Antonio, Tex, June 2008.

Address correspondence to Dr. Brainard (brainard@uga.edu).