title: Dose determination of fondaparinux in healthy cats.
abstract: OBJECTIVE
  To establish practical doses and administration frequencies of fondaparinux for cats that would approximate human therapeutic peak and trough plasma anti-factor Xa activities for thromboprophylaxis (TP) and thrombosis treatment (TT) protocols.
  
  
  METHODS
  6 healthy adult purpose-bred cats.
  
  
  METHODS
  Dosage protocols for TP and TT were selected on the basis of a single compartment pharmacokinetic model incorporating data from humans but modified to account for the higher body weight-normalized cardiac output of cats. Fondaparinux was administered at 0.06 mg/kg, SC, every 12 hours (TP) for 7 days in one session, and 0.20 mg/kg, SC, every 12 hours (TT) for 7 days in another, with a minimum of 1 week separating the sessions. Plasma anti-factor Xa activity was measured before fondaparinux administration (day 1) and at 2 (peak) and 12 (trough) hours after drug administration on days 1 and 7. Platelet aggregation and thromobelastographic (TEG) parameters were also measured 2 hours after drug administration on day 7.
  
  
  RESULTS
  Peak plasma anti-factor Xa activities on day 7 for TP (median, 0.59 mg/L; range, 0.36 to 0.77 mg/L) and TT (median, 1.66 mg/L; range, 1.52 to 2.00 mg/L) protocols were within therapeutic ranges for humans. However, only the TP protocol achieved trough anti-factor Xa activity considered therapeutic in humans (median, 0.19 mg/L; range, 0.00 to 0.37 mg/L) on day 7. There were significant changes in the TEG parameters at peak for the TT protocol, suggesting a hypocoagulable state. No significant changes in platelet aggregation were evident for either protocol.
  
  
  CONCLUSIONS
  A fondaparinux dosage of 0.06 or 0.20 mg/kg, SC, every 12 hours, was sufficient to achieve a peak plasma anti-factor Xa activity in cats that has been deemed therapeutic in humans. This study provided preliminary data necessary to perform fondaparinux dose-determination and clinical efficacy studies.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Nonya N
authors.initials: NN
authors.lastname: Fiakpui
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hogan
authors.forename: Ted
authors.initials: T
authors.lastname: Whittem
authors.forename: Henry W
authors.initials: HW
authors.lastname: Green
authors.forename: Eryn A
authors.initials: EA
authors.lastname: Shipley
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Sederquist
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001792:Blood Platelets / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015951:Factor Xa / Q000187:drug effects / Q000378:metabolism; D005260:Female; D000077425:Fondaparinux; D008297:Male; D011134:Polysaccharides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013916:Thrombelastography / Q000662:veterinary
chemical_list: D000925:Anticoagulants; D011134:Polysaccharides; D015951:Factor Xa; D000077425:Fondaparinux