[en] Species differences in oral bioavailability, first-pass metabolism and pharmacokinetics of biopharmaceutics classification system (BCS) class I compound acetaminophen were studied. The absolute bioavailability was 42.2%, 39.0%, 44.5%, 75.5% and 91.0% in chickens, turkeys, dogs, pigs and horses, respectively. After hydrolysis of metabolites by beta-glucuronidase/sulfatase, apparent bioavailability increased significantly in all species (turkeys: 72.4%, dogs: 100.5%, pigs: 102.2%), except horses (91.6%). Mean metabolic ratios of [acetaminophen glucuronide]/[acetaminophen] between 0 and 1h were significantly higher after oral dosing in turkeys, dogs and pigs, revealing the role of first-pass metabolism in incomplete bioavailability. Evidence of species differences in acetaminophen metabolism is provided by differences in plasma clearance, which was inversely proportional to bioavailability. In conclusion, differences in BA appeared to originate predominantly from differences in first-pass metabolism, demonstrating that the BCS high permeability classification of acetaminophen is consistent across the mammalian species studied. In turkeys, however, incomplete absorption additionally seemed to contribute to the low BA.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Neirinckx, E; Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. eva.neirinckx@ugent.be
Vervaet, C; Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Gent, Belgium
De Boever, S; Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
Remon, J P; Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Gent, Belgium
Gommeren, Kris ; Université de Liège - ULiège > Département clinique des animaux de compagnie et des équidés (DCA) > Pathologie médicale des petits animaux ; Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
Daminet, S; Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
De Backer, P; Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
Croubels, S; Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
Language :
English
Title :
Species comparison of oral bioavailability, first-pass metabolism and pharmacokinetics of acetaminophen.
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