title: Comparison of pharmacokinetics and milk elimination of flunixin in healthy cows and cows with mastitis.
abstract: OBJECTIVE
  To determine whether pharmacokinetics and milk elimination of flunixin and 5-hydroxy flunixin differed between healthy and mastitic cows.
  
  
  METHODS
  Prospective controlled clinical trial.
  
  
  METHODS
  20 lactating Holstein cows.
  
  
  METHODS
  Cows with mastitis and matched control cows received flunixin IV, ceftiofur IM, and cephapirin or ceftiofur, intramammary. Blood samples were collected before (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours after flunixin administration. Composite milk samples were collected at 0, 2, 12, 24, 36, 48, 60, 72, 84, and 96 hours. Plasma and milk samples were analyzed by use of ultra-high-performance liquid chromatography with mass spectrometric detection.
  
  
  RESULTS
  For flunixin in plasma samples, differences in area under the concentration-time curve and clearance were detected between groups. Differences in flunixin and 5-hydroxy flunixin concentrations in milk were detected at various time points. At 36 hours after flunixin administration (milk withdrawal time), 8 cows with mastitis had 5-hydroxy flunixin concentrations higher than the tolerance limit (ie, residues). Flunixin residues persisted in milk up to 60 hours after administration in 3 of 10 mastitic cows.
  
  
  CONCLUSIONS
  Pharmacokinetics and elimination of flunixin and 5-hydroxy flunixin in milk differed between mastitic and healthy cows, resulting in violative residues. This may partially explain the high number of flunixin residues reported in beef and dairy cattle. This study also raised questions as to whether healthy animals should be used when determining withdrawal times for meat and milk.
authors.affiliation: Department of Population Health and Pathobiology and the Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
authors.forename: Lindsey W
authors.initials: LW
authors.lastname: Kissell
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Leavens
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Baynes
authors.forename: Jim E
authors.initials: JE
authors.lastname: Riviere
authors.forename: Geof W
authors.initials: GW
authors.lastname: Smith
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D002417:Cattle; D002511:Cephalosporins / Q000627:therapeutic use; D003002:Clonixin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D008414:Mastitis, Bovine / Q000188:drug therapy / Q000378:metabolism*; D008892:Milk / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002511:Cephalosporins; C014557:flunixin; C053503:ceftiofur; D003002:Clonixin