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Pharmacokinetics Absorption The activity of FLOVENT DISKUS is due to the parent drug, fluticasone propionate. Studies using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (<1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver. In contrast, the majority of the fluticasone propionate delivered to the lung is systemically absorbed. Text Continues Below
The systemic bioavailability of fluticasone propionate from the DISKUS ® device in healthy adult volunteers averages about 18%. Peak steady-state fluticasone propionate plasma concentrations in adult patients with asthma (n = 11) ranged from undetectable to 266 pg/mL after a 500-mcg twice-daily dose of fluticasone 3 propionate inhalation powder using the DISKUS device. The mean fluticasone propionate plasma concentration was 110 pg/mL. Distribution: Following intravenous administration, the initial disposition phase for fluticasone propionate was rapid and consistent with its high lipid solubility and tissue binding. The volume of distribution averaged 4.2 L/kg. The percentage of fluticasone propionate bound to human plasma proteins averages 91%. Fluticasone propionate is weakly and reversibly bound to erythrocytes. Fluticasone propionate is not significantly bound to human transcortin. Metabolism The total clearance of fluticasone propionate is high (average, 1093 mL/min), with renal clearance accounting for less than 0.02% of the total. The only circulating metabolite detected in man is the 17 -carboxylic acid derivative of fluticasone propionate, which is formed through the cytochrome P450 3A4 pathway. This metabolite had less affinity (approximately 1/2000) than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal studies. Other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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