Bioavailability of racemic ketoprofen in healthy horses following rectal administration.
Ketoprofen (KTP) is a chiral non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class, approved by the FDA for the allevation of pain associated with musculoskeletal disorders in horses. The present study was designed to examine the bioavailability of ketoprofen enantiomers after rectal administration of the racemate to healthy horses. One gram of racemic ketoprofen was injected intravenously and administered rectally as a fat based suppository in a cross-over design study (n = 4). Blood samples were analysed for KTP enantiomers using HPLC. After IV administration, the S(+) enantiomer concentrations in plasma were higher than the R(-) enantiomer concentrations and the AUC(0-12 h) for the S(+) enantiomer was significantly higher than for the R(-) enantiomer. Following rectal administration C(max) and AUC(0-12 h) were significantly higher for the S(+) than for the R(-) enantiomer. Bioavailability after rectal administration was low. Since there was no significant difference in bioavailability between the two enantiomers, it is assumed that no pre-systemic inversion from R(-) to S(+) occurred after rectal administration of racemic KTP to horses.
Corveleyn
S
S
Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, University of Gent, Harelbekestraat 72, Gent, 9000, Belgium.
Henrist
D
D
Remon
J P
JP
Van Der Weken
G
G
Baeyens
W
W
Haustraete
J
J
Aboul-Enein
H Y
HY
Sustronck
B
B
Deprez
P
P
D000285:Administration, Rectal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D006736:Horses / Q000378:metabolism*; D007536:Isomerism; D007660:Ketoprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007660:Ketoprofen