title: Randomised trial of the bioavailability and efficacy of orally administered flunixin, carprofen and ketoprofen in a pain model in sheep.
abstract: OBJECTIVE
  To determine the efficacy and bioavailability of non-steroidal anti-inflammatory drugs (NSAIDs) when administered orally to sheep.
  
  
  METHODS
  Randomised experimental design with four treatment groups: three NSAID groups and one control group (n = 10/group). The study animals were 40 18-month-old Merino ewes with an average weight of 31.4 ± 0.5 kg.
  
  
  METHODS
  Treatment was given orally at 24 h intervals for 6 days at dose rates expected to achieve therapeutic levels in sheep: carprofen (8.0 mg/kg), ketoprofen (8.0 mg/kg) and flunixin (4.0 mg/kg). Oil of turpentine (0.1 mL) was injected into a forelimb of each sheep to induce inflammation and pain; responses (force plate pressure, skin temperature, limb circumference, haematology and plasma cortisol) were measured at 0, 3, 6, 9, 12, 24, 36, 48, 72 and 96 h post-injection. NSAID concentrations were determined by ultra-high-pressure liquid chromatography.
  
  
  RESULTS
  The NSAIDs were detectable in ovine plasma 2 h after oral administration, with average concentrations of 4.5-8.4 µg/mL for ketoprofen, 2.6-4.1 µg/mL for flunixin and 30-80 µg/mL for carprofen. NSAID concentrations dropped 24 h after administration. Pain response to an oil of turpentine injection was assessed using the measures applied but no effect of the NSAIDs was observed. Although this pain model has been previously validated, the responses observed in this study differed from those in the previous study.
  
  
  CONCLUSIONS
  The three NSAIDs reached inferred therapeutic concentrations in blood at 2 h after oral administration. The oil of turpentine lameness model may need further validation.
authors.affiliation: CSIRO, FD McMaster Laboratory, New England Highway, Armidale, New South Wales, Australia. danila.marini@csiro.au.|School of Environmental and Rural Sciences, The University of New England, Armidale, NSW, Australia. danila.marini@csiro.au.
authors.forename: D
authors.initials: D
authors.lastname: Marini
authors.affiliation: PIA PHARMA, Gladesville, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Pippia
authors.affiliation: CSIRO, FD McMaster Laboratory, New England Highway, Armidale, New South Wales, Australia.
authors.forename: I G
authors.initials: IG
authors.lastname: Colditz
authors.affiliation: School of Environmental and Rural Sciences, The University of New England, Armidale, NSW, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Hinch
authors.affiliation: Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: J C
authors.initials: JC
authors.lastname: Petherick
authors.affiliation: CSIRO, FD McMaster Laboratory, New England Highway, Armidale, New South Wales, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D003002:Clonixin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D015331:Cohort Studies; D004195:Disease Models, Animal; D005260:Female; D005552:Forelimb; D006854:Hydrocortisone / Q000097:blood; D007509:Irritants / Q000009:adverse effects; D007660:Ketoprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D007794:Lameness, Animal / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy / Q000662:veterinary*; D012756:Sheep; D014425:Turpentine / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D007509:Irritants; C014557:flunixin; D007660:Ketoprofen; C007005:carprofen; D003002:Clonixin; D006854:Hydrocortisone; D014425:Turpentine
keywords: animal welfare; non-steroidal anti-inflammatory drugs; pain; sheep