Bioavailability of racemic ketoprofen in healthy horses following rectal administration

Ketoprofen (KTP) is a chiral non-steroidal anti-inflammatory drug (NSAID) o f 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 rec tal administration of the racemate to healthy horses. One gram of racemic k etoprofen was injected intravenously and administered rectally as a fat bas ed suppository in a cross-over design study (n = 4). Blood samples were ana lysed for KTP enantiomers using HPLC. After IV administration, the S(+) ena ntiomer concentrations in plasma were higher than the R(-) enantiomer conce ntrations and the AUC(0-12 h) for the S(+) enantiomer was significantly hig her 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(-) enant iomer. 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 aft er octal administration of racemic KTP to horses. (C) 1999 Harcourt Publish ers Limited.