Species comparison of enantioselective oral bioavailability and pharmacokinetics of ketoprofen.
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.
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. eva.neirinckx@ugent.be
E
E
Neirinckx
S
S
Croubels
S
S
De Boever
J P
JP
Remon
T
T
Bosmans
S
S
Daminet
P
P
De Backer
C
C
Vervaet
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D007660:Ketoprofen / Q000097:blood / Q000493:pharmacokinetics*; D013045:Species Specificity
D007660:Ketoprofen