Pharmacodynamic and pharmacokinetic evaluation of clopidogrel and the carboxylic acid metabolite SR 26334 in healthy dogs.
OBJECTIVE
To determine pharmacodynamic and pharmacokinetic properties of clopidogrel and the metabolite SR 26334 in dogs.


METHODS
9 mixed-breed dogs.


METHODS
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 microg/mL) was detected 1 hour after administration.


CONCLUSIONS
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.
Brainard
Benjamin M
BM
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. brainard@uga.edu
Kleine
Stephanie A
SA
Papich
Mark G
MG
Budsberg
Steven C
SC
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002264:Carboxylic Acids / Q000378:metabolism; D000077144:Clopidogrel; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D012016:Reference Values; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D002264:Carboxylic Acids; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; D013988:Ticlopidine