Randomised trial of the bioavailability and efficacy of orally administered flunixin, carprofen and ketoprofen in a pain model in sheep

Marini, Danila; Pippia, Joe; Colditz, Ian G.; Hinch, G. N.; Petherick, J. Carol; C, Lee

doi:10.1111/avj.12351

Cited by 14 publications

(12 citation statements)

References 36 publications

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“…Concentrations measured in this study were somewhat lower compared with those reported in our previous study (Marini et al, 2015) where flunixin concentration in plasma reached values between 2.6 -4.1 µg/mL 2 h after a single oral dose (4 mg/kg) in sheep. Reports of therapeutic concentrations of flunixin in farm animals are limited, however, Toutain et al, (1994) reported therapeutic effects in horses when plasma concentrations reached 0.2 -0.9 µg/mL.…”

Section: Discussioncontrasting

confidence: 91%

Peer Review #1 of "Palatability and pharmacokinetics of flunixin when administered to sheep through feed (v0.2)"

2016

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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.

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Section: Discussioncontrasting

confidence: 91%

Peer Review #1 of "Palatability and pharmacokinetics of flunixin when administered to sheep through feed (v0.2)"

2016

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“…When consuming feed ad-libitum, the majority of sheep (7 out of 8) achieved plasma flunixin concentrations above 1.0 µg/mL within 2 h of consuming medicated feed, with maximum concentrations (between 1.33 and 2.80 µg/mL) being reached on average by 6 h. Concentrations observed in this current study were somewhat less to those reported in our previous study (Marini et al 2015) where flunixin concentration in plasma reached between 2.6 -4.1 µg/mL 2 h after a single oral dose (4mg/kg) in sheep. Reports of therapeutic concentrations of flunixin in farm animals are limited, however, Toutain et al (1994) reported therapeutic effects in horses when plasma concentrations reached 0.2-0.9 µg/mL.…”

Section: Discussioncontrasting

confidence: 92%

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Supplemental Information 2: Palatability Trial Raw Data

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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 13.62 ± 1.17 h. Sheep did not show aversiveness to pellets supplemented with flunixin. When consuming medicated feed ad libitum all sheep were able to obtain inferred therapeutic concentrations of flunixin in plasma within 6 h. Provision of flunixin in the feed may provide a practical way to provide pain relief to sheep and lambs following painful husbandry procedures removing the need for multiple injections, reducing handling stress and minimising labour requirements.

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“…A randomised trial looks at the bioavailability and efficacy of flunixin, carprofen and ketoprofen in a model of pain in sheep . Although there is little data on the use of NSAIDs in sheep, if these anti‐inflammatories could be given orally and incorporated into feed, they could be used by producers.…”

Section: Production Animalsmentioning

confidence: 99%

In this issue – August 2015

2015

Aust Veterinary J

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Randomised trial of the bioavailability and efficacy of orally administered flunixin, carprofen and ketoprofen in a pain model in sheep

Abstract: 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.

Cited by 14 publications

References 36 publications

Peer Review #1 of "Palatability and pharmacokinetics of flunixin when administered to sheep through feed (v0.2)"

Peer Review #1 of "Palatability and pharmacokinetics of flunixin when administered to sheep through feed (v0.2)"

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In this issue – August 2015

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