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.


METHODS
8 crossbred pigs.


METHODS
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 microg/mL and 7.62 +/- 1.22 microg/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
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.
Raekallio
Marja R
MR
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, PO Box 57, University of Helsinki, Fl-00014 Helsinki, Finland.
Mustonen
Katja M
KM
Heinonen
Mari L
ML
Peltoniemi
Olli A T
OA
Säkkinen
Mia S
MS
Peltoniemi
S Marikki
SM
Honkavaara
Juhana M
JM
Vainio
Outi M
OM
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007660:Ketoprofen / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D013552:Swine / Q000097:blood* / Q000378:metabolism*; D013810:Therapeutic Equivalency
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007660:Ketoprofen