title: Effect of flunixin meglumine and firocoxib on ex vivo cyclooxygenase activity in horses undergoing elective surgery.
abstract: OBJECTIVE
  To evaluate ex vivo cyclooxygenase (COX) inhibition and compare in vitro and ex vivo COX-1 inhibition by flunixin meglumine and firocoxib in horses.
  
  
  METHODS
  4 healthy horses for in vitro experiments and 12 healthy horses (6 males and 6 females; 5 Thoroughbreds, 5 Warmbloods, and 2 ponies) undergoing elective surgery for ex vivo experiments.
  
  
  METHODS
  12 horses received flunixin meglumine (1.1 mg/kg, IV, q 12 h) or firocoxib (0.09 mg/kg, IV, q 24 h). Blood samples were collected before (baseline) and 2 and 24 hours after NSAID administration. Prostanoids (thromboxane B2, prostaglandin E2, and prostaglandin E metabolites) served as indicators of COX activity, and serum drug concentrations were measured by use of high-performance liquid chromatography. An in vitro coagulation-induced thromboxane B2 assay was used to calculate drug concentration-COX-1 inhibition curves. Effect of time and treatment on COX activity was determined. Agreement between in vitro and ex vivo measurement of COX activity was assessed with Bland-Altman analysis.
  
  
  RESULTS
  At 2 and 24 hours after NSAID administration, COX-1 activity was reduced, compared with baseline activity, for the flunixin meglumine group only and relative COX-1 activity was significantly greater for the firocoxib group, compared with that for the flunixin meglumine group. There was no significant change in COX-2 activity after surgery for either group. Bland-Altman analysis revealed poor agreement between in vitro and ex vivo measurement of COX-1 activity.
  
  
  CONCLUSIONS
  Compared with flunixin meglumine, firocoxib had COX-1-sparing effects ex vivo in equine patients that underwent elective surgery.
authors.affiliation: Boyd Orr Centre for Population and Ecosystem Health, School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, Scotland.
authors.forename: Marco
authors.initials: M
authors.lastname: Duz
authors.forename: Tim D
authors.initials: TD
authors.lastname: Parkin
authors.forename: Rose M
authors.initials: RM
authors.lastname: Cullander
authors.forename: John F
authors.initials: JF
authors.lastname: Marshall
mesh_terms: D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D003002:Clonixin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D017558:Elective Surgical Procedures / Q000662:veterinary; D005260:Female; D006736:Horses / Q000097:blood / Q000601:surgery*; D008297:Male; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013450:Sulfones; C014558:flunixin meglumine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015107:4-Butyrolactone; D003002:Clonixin; C487384:firocoxib