title: Pharmacodynamic and pharmacokinetic evaluation of clopidogrel and the carboxylic acid metabolite SR 26334 in healthy dogs.
abstract: 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.
authors.affiliation: Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. brainard@uga.edu
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Brainard
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Kleine
authors.forename: Mark G
authors.initials: MG
authors.lastname: Papich
authors.forename: Steven C
authors.initials: SC
authors.lastname: Budsberg
mesh_terms: 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
chemical_list: D002264:Carboxylic Acids; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; D013988:Ticlopidine