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 nonsteroidal anti-inflammatory drugs (NSAIDs) when administered orally to sheep. 'Design' 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 (8.0mg/kg), ketoprofen (8.0mg/kg) and flunixin (4.0mg/kg). Oil of turpentine (0.1mL) 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 and clinical relevance' 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.