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

Marja R. RaekallioDepartment of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, PO Box 57, University of Helsinki, Fl-00014 Helsinki, Finland.

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Katja M. MustonenVetcare Ltd, PO Box 99, FI-24101 Salo, Finland.

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Mari L. HeinonenDepartment of Production Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, FI-04920 Saarentaus, Finland.

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Olli A. T. PeltoniemiDepartment of Production Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, FI-04920 Saarentaus, Finland.

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Mia S. SäkkinenDivision of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Helsinki, FI-04920 Saarentaus, Finland.

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S. Marikki PeltoniemiDivision of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Helsinki, FI-04920 Saarentaus, Finland.

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Juhana M. HonkavaaraDepartment of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, PO Box 57, University of Helsinki, Fl-00014 Helsinki, Finland.

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Outi M. VainioDepartment of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, PO Box 57, University of Helsinki, Fl-00014 Helsinki, Finland.

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Abstract

Objective—To assess bioequivalence after oral, IM, and IV administration of racemic ketoprofen in pigs and to investigate the bioavailability after oral and IM administration.

Animals—8 crossbred pigs.

Procedures—Each pig received 4 treatments in a randomized crossover design, with a 6-day washout period. Ketoprofen was administered at 3 and 6 mg/kg, PO; 3 mg/kg, IM; and 3 mg/kg, IV. Plasma ketoprofen concentrations were measured by use of high-performance liquid chromatography for up to 48 hours. To assess bioequivalence, a 90% confidence interval was calculated for the area under the time-concentration curve (AUC) and maximum plasma concentration (Cmax).

Results—Equivalence was not detected in the AUCs among the various routes of administration nor in Cmax between oral and IM administration of 3 mg/kg. The bioavailability of ketoprofen was almost complete after each oral or IM administration. Mean ± SD Cmax was 5.09 ± 1.41 μg/mL and 7.62 ± 1.22 μg/mL after oral and IM doses of 3 mg/kg, respectively. Mean elimination half-life varied from 3.52 ± 0.90 hours after oral administration of 3 mg/kg to 2.66 ± 0.50 hours after IV administration. Time to peak Cmax after administration of all treatments was approximately 1 hour. Increases in AUC and Cmax were proportional when the orally administered dose was increased from 3 to 6 mg/kg.

Conclusions and Clinical Relevance—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.

Abstract

Objective—To assess bioequivalence after oral, IM, and IV administration of racemic ketoprofen in pigs and to investigate the bioavailability after oral and IM administration.

Animals—8 crossbred pigs.

Procedures—Each pig received 4 treatments in a randomized crossover design, with a 6-day washout period. Ketoprofen was administered at 3 and 6 mg/kg, PO; 3 mg/kg, IM; and 3 mg/kg, IV. Plasma ketoprofen concentrations were measured by use of high-performance liquid chromatography for up to 48 hours. To assess bioequivalence, a 90% confidence interval was calculated for the area under the time-concentration curve (AUC) and maximum plasma concentration (Cmax).

Results—Equivalence was not detected in the AUCs among the various routes of administration nor in Cmax between oral and IM administration of 3 mg/kg. The bioavailability of ketoprofen was almost complete after each oral or IM administration. Mean ± SD Cmax was 5.09 ± 1.41 μg/mL and 7.62 ± 1.22 μg/mL after oral and IM doses of 3 mg/kg, respectively. Mean elimination half-life varied from 3.52 ± 0.90 hours after oral administration of 3 mg/kg to 2.66 ± 0.50 hours after IV administration. Time to peak Cmax after administration of all treatments was approximately 1 hour. Increases in AUC and Cmax were proportional when the orally administered dose was increased from 3 to 6 mg/kg.

Conclusions and Clinical Relevance—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.

Contributor Notes

Supported by Vetcare Limited.

The authors thank Katri Koski and Erja Piitulainen for assistance with high-performance liquid chromatography assays and Elina Viitasaari and Laura Malinen for assistance with collection and preparation of blood samples.

Address correspondence to Dr. Raekallio.