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- W2167176353 abstract "The purpose of this study was to investigate the metabolism and disposition of fluticasone furoate, an enhanced-affinity glucocorticoid receptor agonist, in humans. In a two-part, open-label design study, five healthy male subjects received a p.o. dose of 2 mg of [(14)C]fluticasone furoate, followed 4 weeks later by an i.v. dose of 0.25 mg of [(14)C]fluticasone furoate (as a 30-min infusion). Oral absorption was rapid and estimated at approximately 30%, although the oral bioavailability was markedly lower at 1.6%, limited by extensive first-pass metabolism. Plasma clearance was 58.3 l/h, with a volume of distribution of 642 liters and a terminal elimination half-life of 15.3 h. The major circulating component identified in plasma extracts after i.v. and p.o. dosing was unchanged parent compound, with 17beta-carboxylic acid (GW694301X; M10) also being notable after p.o. administration. Mean recovery of radioactivity was approximately 92 and 102% at 216 and 168 h after i.v. and p.o. administration, respectively, with most (at least 90%) recovered in the feces. Fluticasone furoate was extensively metabolized, with only trace amounts of unchanged parent compound observed in feces following either route of administration. The predominant pathway was removal of the S-fluoromethyl carbothioate group to yield GW694301X (M10). Other pathways included oxidative defluorination to yield a hydroxyl at the C6 position. There was no evidence for metabolic loss of the furoate group from fluticasone furoate or any of its metabolites. Evidence presented suggests that enterocytes have a role in the metabolism of unabsorbed fluticasone furoate." @default.
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- W2167176353 date "2008-08-11" @default.
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- W2167176353 title "Metabolism and Disposition of Fluticasone Furoate, an Enhanced-Affinity Glucocorticoid, in Humans" @default.
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- W2167176353 doi "https://doi.org/10.1124/dmd.108.022137" @default.
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