Bioavailability and efficacy of orally administered flunixin, carprofen and ketoprofen in a pain model in sheep

The pain from routine husbandry practices performed on sheep can last several days and sheep often don't receive therapeutic interventions to provide pain relief. Attractive candidates for long-acting pain relief are non-steroidal anti-inflammatory drugs (NSAIDs). If NSAIDs can be shown to alleviate pain and inflammation when administered orally in sheep, they could be incorporated in feed, providing producers with a practical method to provide long-term pain relief in sheep. The aim of this research was to test the bioavailability and efficacy of carprofen, ketoprofen and flunixin administered orally using a lameness model (turpentine (0.1 ml) injected into one forelimb) developed to enable objective quantitative assessment of the analgesic, antipyretic and anti-inflammatory actions of NSAIDs in sheep

Palatability and pharmacokinetics of flunixin when administered to sheep through feed

Applying analgesics to feed is a potentially easy method of providing pain-relief to sheep and lambs that undergo painful husbandry procedures. To be effective, the medicated feed needs to be readily accepted by sheep and its consumption needs to result in therapeutic concentrations of the drug. In the present experiment, pelleted feed was supplemented with flunixin (4.0 mg/kg live weight) and offered to eight sheep. To test the palatability of flunixin, the individually penned sheep were offered normal feed and feed supplemented with flunixin in separate troughs for two consecutive days. A trend for a day by feed-type (control versus flunixin supplemented) interaction suggested that sheep may have had an initial mild aversion to pellets supplemented with flunixin on the first day of exposure, however, by on the second day there was no difference in consumption of normal feed and feed supplemented with flunixin. To test pharmacokinetics, sheep were offered 800 g of flunixin supplemented feed for a 12 h period. Blood samples were taken over 48 h and plasma drug concentrations were determined using ultra-high-pressure liquid chromatography, negative electrospray ionisation and tandem mass spectrometry. The mean ± S.D. time required to reach maximum concentration was 6.00 ± 4.14 h and ranged from 1 to 12 h. Average maximum plasma concentration was 1.78 ± 0.48 µg/mL and ranged from 1.61 to 2.80 µg/mL. The average half-life of flunixin was 7.95 ± 0.77 h and there was a mean residence time of 13.62 ± 1.17 h. Free access to flunixin supplemented feed enabled all sheep to obtain inferred therapeutic concentrations of flunixin in plasma within 6 h of starting to consume the feed. Provision of an analgesic in feed may be an alternative practical method for providing pain relief to sheep