Evaluation of bioequivalence after oral, intramuscular, and intravenous administration of racemic ketoprofen in pigs

Raekallio, Marja; Mustonen, K.; Heinonen, Mari; Peltoniemi, Olli; Säkkinen, Mia Susanna; Peltoniemi, S. Marikki; Honkavaara, Juhana; Vainio, Outi

doi:10.2460/ajvr.69.1.108

Cited by 21 publications

(28 citation statements)

References 30 publications

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“…A vinyl tube (inner diameter, 1.0 mm; outer diameter 1.5 mm, Biocorp Australia Pty Ltd, Australia) for blood sampling was inserted nonsurgically into the ear vein or vena cephalica one day before the first sampling [5]. During the wash-out period, the vinyl tubes were flushed with heparinized saline twice a day to prevent blood clots forming inside them.…”

Section: Methodsmentioning

confidence: 99%

“…As ketoprofen pharmacokinetics is linear [5], the dose was normalized (AUC norm = (D im /D po ) x AUC po ) when AUCs were statistically compared between administration groups. Differences were considered significant at P < 0.05.…”

Section: Methodsmentioning

confidence: 99%

“…The oral solution has marketing authorization in several EU countries [3] for the treatment of fever and dyspnea associated with respiratory disease in fattening pigs at a dose rate of 1.5–3 mg/kg [4]. Orally administered racemic ketoprofen was reported to be absorbed well in pigs, and bioavailability was almost complete [5]. It also alleviated the signs of non-infectious lameness in sows [6].…”

Section: Introductionmentioning

confidence: 99%

“…However, in rats and cats, enantioselective pharmacokinetics were influenced by the oral route of administration compared to intravenous administration [21,23], whereas in elephants there were no significant differences [24]. In our previous study a second peak in total ketoprofen concentrations in plasma was observed in pigs [5], which may indicate enterohepatic circulation of the drug. Stereoselective enterohepatic circulation of ketoprofen has been reported to exist in rats [25].…”

Section: Introductionmentioning

confidence: 99%

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Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

et al. 2012

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BackgroundKetoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO) and intra muscular (IM) routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers between those routes of administration in growing pigs.MethodsEleven pigs received racemic ketoprofen at dose rates of 4 mg/kg PO and 3 mg/kg IM in a randomized, crossover design with a 6-day washout period. Enantiomers were separated on a chiral column and their concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated and relative bioavailability (Frel) was determined for S and R –ketoprofen.ResultsS-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The mean (± SD) maximum S-ketoprofen concentration in plasma (7.42 mg/L ± 2.35 in PO and 7.32 mg/L ± 0.75 in IM) was more than twice as high as that of R-ketoprofen (2.55 mg/L ± 0.99 in PO and 3.23 mg/L ± 0.70 in IM), and the terminal half-life was three times longer for S-ketoprofen (3.40 h ± 0.91 in PO and 2.89 h ± 0.85 in IM) than R-ketoprofen (1.1 h ± 0.90 in PO and 0.75 h ± 0.48 in IM). The mean (± SD) relative bioavailability (PO compared to IM) was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively.ConclusionsAlthough some minor differences were detected in the ketoprofen enantiomer concentrations in plasma after PO and IM administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen should be comparable after intramuscular and oral routes of administration in growing pigs.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

et al. 2012

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“…It was shown to be effective in treating lameness in sows [16], and improved feed intake in sows after farrowing [9] and in pigs challenged with Actinobacillus pleuropneumoniae [17]. It is well absorbed after intramuscular injection [18].…”

Section: Introductionmentioning

confidence: 98%

The effect of ketoprofen on feeding behavior of tail-bitten pigs

et al. 2015

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No research has been reported on the effect of intramuscular ketoprofen administration on the feeding behavior of tail-bitten pigs. In order to investigate this, a longitudinal, double blind, placebo-controlled field trial was conducted with a total of 77 pigs from a finishing herd. Pigs received either ketoprofen (KET) or a placebo (PLAC) intramuscularly for three days and procaine penicillin for five days after the tail was first observed to be damaged. Pigs were followed from day −2 to day 3 with respect to a noted tail wound. Only new incidence of tail biting was included. Nine to 11 pigs per pen were reared with a single automatic feeder. A transponder attached to the ear of each pig recorded times of entrance and exit to the feeder and feed consumed. To calculate average daily weight gain (ADG), pigs were weighed at days 0, 6 and 13. Time spent at the feeder by visit and on a daily basis, and mean daily intervals between feeder visits per pig were computed in minutes. Daily feeding rate (FR) was calculated from the feeder data (consumed feed (g) / time at the feeder (s)). Placebo pigs consumed more feed and spent more time at the feeder on day 1 than KET pigs (P < 0.05). For all pigs, FR increased from day 1 to day 3 (P < 0.05). Feeder visit intervals were longer and frequency lower on day 0 compared with other days (P < 0.05). Average feed consumption and time spent at the feeder per day decreased on day 0 and returned to the initial level on day 1 (P < 0.05 for both). No effect on ADG was recorded. Intramuscular administration of ketoprofen induced little change in feeding behavior and had no effect on weight gain. Placebo-treated pigs may have used feed as an analgesic and calming substance to some degree, leading to temporarily increased feed consumption.

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Non‐Steroidal Anti‐Inflammatory Drugs

Willette

2024

Pharmacology in Veterinary Anesthesia and Analgesia

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Evaluation of bioequivalence after oral, intramuscular, and intravenous administration of racemic ketoprofen in pigs

Abstract: Orally administered ketoprofen was absorbed well in pigs, although bioequivalence with IM administration of ketoprofen was not detected. Orally administered ketoprofen may have potential for use in treating pigs.

Cited by 21 publications

References 30 publications

Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

The effect of ketoprofen on feeding behavior of tail-bitten pigs

Non‐Steroidal Anti‐Inflammatory Drugs

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