Species comparison of enantioselective oral bioavailability and pharmacokinetics of ketoprofen |
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Authors: | Neirinckx E Croubels S De Boever S Remon J P Bosmans T Daminet S De Backer P Vervaet C |
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Institution: | aDepartment of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium;bLaboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Gent, Belgium;cDepartment of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium |
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Abstract: | As a part of ongoing research to further elucidate frequent and species-specific causes of differences in oral bioavailability, a 3 mg/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. |
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Keywords: | Ketoprofen Enantiomers Bioavailability Pharmacokinetics Species differences |
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