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

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 (C-max) Results - Equivalence was not detected in the AUCs among the various routes of administration nor in C-max between oral and IM administration of 3 mg/kg. The bioavailability of ketoprofen was almost complete after each oral or IM administration. Mean +/- SD C-max was 5.09 +/- 1.41 mu g/mL and 762 +/- 1.22 mu g/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 C-max after administration of all treatments was approximately 1 hour. Increases in AUC and C-max 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.