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.
Neirinckx
E
E
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. eva.neirinckx@ugent.be
Croubels
S
S
De Boever
S
S
Remon
J P
JP
Bosmans
T
T
Daminet
S
S
De Backer
P
P
Vervaet
C
C
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