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The systemic bioavailability of fluticasone propionate inhalation aerosol in healthy volunteers averaged about 30% of the dose delivered from the actuator. Peak plasma concentrations after an 880-mcg inhaled dose ranged from 0.1 to 1.0 ng/ 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 averaged 91%. Fluticasone propionate is weakly and reversibly bound to erythrocytes. Fluticasone propionate is not significantly bound to human transcortin. Metabolism: Text Continues Below
The total clearance of fluticasone propionate is high (average, 1,093 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 approximately 2,000 times less affinity 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. Excretion Following intravenous dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of approximately 7.8 hours. Less than 5% of a radiolabeled oral dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites. Special Populations: Formal pharmacokinetic studies using fluticasone propionate were not carried out in any special populations. In a clinical study using fluticasone propionate inhalation powder, trough fluticasone propionate plasma concentrations were collected in 76 males and 74 females after inhaled administration of 100 and 500 mcg twice daily. Full pharmacokinetic profiles were obtained from 7 female patients and 13 male patients at these doses, and no overall differences in pharmacokinetic behavior were found. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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