Determination of concentrations of ketoprofen, carprofen and flunixin in plasma of sheep following oral administration in a pain model conducted in sheep

Summary

​A sensitive and selective analytical method for the determination of ketoprofen, carprofen, flunixin and metabolite 5-hydroxyflunixin in ovine plasma was developed and validated. Sheep were randomised into 4 treatment groups, with a placebo group receiving saline and 3 groups given NSAIDs orally for 6 days. NSAIDs were given at approximately double the dose rate used for non-parenteral administration to cattle and previously used experimentally in sheep every 24 hours: carprofen (8.0 mg/kg), ketoprofen (8.0 mg/kg) and flunixin (4.0 mg/kg). Carprofen, ketoprofen and flunixin were all present in ovine plasma two hours after oral administration, with averages between 4.5 - 8.4µg/mL for ketoprofen, 2.6 - 4.1µg/mL for flunixin, 0.1 - 0.78µg/mL for 5-hydroxyflunixin and 30 - 80µg/mL for carprofen. NSAID concentrations dropped 24 h after administration. The three NSAIDs were bioavailable in sheep two hours after oral administration with carprofen and flunixin reaching inferred therapeutic concentrations in blood by this time. ​