Species comparison of enantioselective oral bioavailability and pharmacokinetics of ketoprofen

Res Vet Sci. 2011 Dec;91(3):415-21. doi: 10.1016/j.rvsc.2010.08.017. Epub 2010 Oct 18.

Abstract

As a part of ongoing research to further elucidate frequent and species-specific causes of differences in oral bioavailability, a 3mg/kg dose of racemic ketoprofen, a high permeability/low solubility compound in the human biopharmaceutics classification system, was administered intravenously and orally to different species. Due to possible enantioselective disposition kinetics and inversion, enantiomers were quantitated separately using a stereospecific HPLC assay. The absolute bioavailability of R(-) and S(+) ketoprofen in chickens, turkeys, dogs and pigs was 31.5% and 52.6%, 42.6% and 32.5%, 33.6% and 89.1%, and 85.9% and 83.5% respectively. Incomplete bioavailability in poultry is probably due to incomplete absorption in addition to first-pass elimination. Low bioavailability of R(-) ketoprofen in dogs, strongly indicates first-pass metabolism. High bioavailability of S(+) ketoprofen in dogs and both enantiomers in pigs confirms that absorption of these substances is complete and controlled by gastric emptying rather than dissolution.

MeSH terms

  • Animals
  • Area Under Curve
  • Biological Availability
  • Cross-Over Studies
  • Female
  • Half-Life
  • Ketoprofen / blood
  • Ketoprofen / pharmacokinetics*
  • Species Specificity

Substances

  • Ketoprofen