Background: Safety of meloxicam, a potent NSAID with selective COX-2 inhibition, has not been evaluated in horses. Objectives: To evaluate pharmacokinetics and safety of single and repeated oral doses of meloxicam in adult horses. Animals: Forty-nine healthy, university-owned adult lightbreed horses. Methods: Study conducted in 2 parts. Part I addressed pharmacokinetics of single oral dose meloxicam (0.6 mg/kg) in 16 horses. Part II, 33 horses were randomly assigned to 5 treatment groups to assess prolonged administration (0.6 mg/kg PO q24h for 6 weeks, n = 7) or higher doses (1.8 mg/kg, n = 7, or 3.0 mg/kg PO q24h, n = 7) of meloxicam for 2 weeks, compared with control horses (placebo, n = 7, or phenylbutazone, 4.4 mg/kg q12h on day 1, 2.2 mg/kg q12h for 4 days, then 2.2 mg/kg q24h for 9 days, n = 5).Results: Maximum plasma concentration following a single oral dose of meloxicam was 915.1 ± 116.9 ng/mL and elimination half-life 10.2 ± 3.0 hours. Meloxicam (0.6 mg/kg, q24h, PO for 6 weeks) yielded plasma concentrations between 100 and 1000 ng/mL and was well tolerated by healthy adult horses. Administration of 3-5 times the recommended dose of meloxicam was associated with decreased total serum protein and albumin concentrations, gastrointestinal damage, renal damage, or bone marrow dyscrasia. PBZ administration was associated with the development right dorsal colitis, gastric ulceration, and protein losing enteropathy in 2 horses.Conclusions and Clinical Importance: Administration meloxicam at 0.6 mg/kg q24h was well tolerated for 6 weeks, without drug accumulation in plasma. Higher doses were associated with dose-dependent adverse effects typical of class of drugs.

Background: The pharmacokinetics, efficacy, and safety of meloxicam have been evaluated in adult horses, but not foals. Physiologic differences between neonates and adults might alter drug pharmacokinetics and therapeutic index.Hypotheses: The pharmacokinetics of meloxicam will be different in foals compared with adult horses, and foals could be at increased risk for adverse drug effects.Animals: Twenty lightbreed foals less than 6 weeks of age at commencement of the study. Methods: Single and repeated oral dose pharmacokinetics were determined for meloxicam (0.6 mg/kg) in 10 foals. The safety of the drug was further evaluated in a 2nd group of 10 foals in a randomized blinded prospective study.Results: Plasma concentrations after a single oral dose of meloxicam (0.6 mg/kg) and time to maximum plasma concentration were similar to adult horses. However, drug clearance was much more rapid in foals (elimination half-life 2.48 AE 0.25 hours). Administration of 0.6 mg/kg every 12 hours was well tolerated by foals for up to 3 weeks, with no evidence of drug accumulation in plasma. Adverse effects observed in adult horses at higher dose rates were not observed in foals given 1.8 mg/kg twice daily for 7 days.Conclusions and clinical importance: Meloxicam at an oral dose rate of 0.6 mg/kg every 12 hours provided plasma concentrations likely to be therapeutic. In contrast to findings for other NSAIDs, foals appeared more resilient to the adverse effects of this drug than was observed in adult horses.

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.

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.

Applying analgesics to feed is a potentially easy method of providing pain-relief to sheep and lambs that undergo painful husbandry procedures. In order for sheep to consume medicated feed it needs to be know if the medication has an adverse odour or flavour that may affect consumption. It is also important to determine if therapeutic concentrations of a non-steroidal anti-inflammatories (NSAIDs) can be achieved when administered to sheep as a feed supplement. Pelleted feed was supplemented with flunixin (4.0mg/kg liveweight) and administered to eight sheep, which they were able to consume over a 12 h period.Blood samples were taken over 48 h and plasma drug concentrations were determined using Ultra High Pressure Liquid Chromatography. The mean time required to reach maximum concentration was 6 ± 1.46 h and ranged from 1 to 12 h. Average maximum plasma concentration was 1.78 ± 0.17µg/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 retention time of 21 Applying analgesics to feed is a potentially easy method of providing pain-relief to sheep and 22 lambs that undergo painful husbandry procedures. In order for sheep to consume medicated feed 23 it needs to be know if the medication has an adverse odour or flavour that may affect 24 consumption. It is also important to determine if therapeutic concentrations of a non-steroidal 25 anti-inflammatories (NSAIDs) can be achieved when administered to sheep as a feed 26 supplement. Pelleted feed was supplemented with flunixin (4.0mg/kg liveweight) and 27 administered to eight sheep, which they were able to consume over a 12 h period. Blood samples 28 were taken over 48 h and plasma drug concentrations were determined using Ultra High Pressure 29 Liquid Chromatography. The mean time required to reach maximum concentration was 6 ± 1.46 30 h and ranged from 1 to 12 h. Average maximum plasma concentration was 1.78 ± 0.17µg/mL 31 and ranged from 1.61 to 2.80 µg/mL. The average half-life of flunixin was 7.95 ± 0.77 h and 32 there was a mean retention time of 13.62 ± 1.17 h. Sheep did not show aversiveness to pellets 33 supplemented with flunixin. When consuming medicated feed ad libitum all sheep were able to 34 obtain inferred therapeutic concentrations of flunixin in plasma within 6 h. Provision of flunixin 35 in the feed may provide a practical way to provide pain relief to sheep and lambs following 36 painful husbandry procedures removing the need for multiple injections, reducing handling stress 37 and minimising labour requirements. 44 Flunixin meglumine is a potent non-steroidal anti-inflammatory (NSAID) that is commonly used 45 in veterinary medicine for its anti-inflammatory, analgesic and antipyretic activity. Like other 46 NSAIDs, flunixin reduces inflammation by inhibiting cyclooxygenase and, in turn, decreasing 47 the production of prostaglandin (Cheng et al. 1998b), an important inflammatory mediator. 48 Flunixin is known to be effective at relieving pain in various domesticated species such as h...