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Clinical Pharmacology
CLINICAL PHARMACOLOGY
Fluticasone propionate is a synthetic, trifluorinated glucocorticoid with potent anti-inflammatory activity. In vitro assays using human lung cytosol preparations have established fluticasone propionate as a human glucocorticoid receptor agonist with an affinity 18 times greater than dexamethasone, almost twice that of beclomethasone-17-monopropionate (BMP), the active metabolite of beclomethasone dipropionate, and over 3 times that of budesonide. Data from the McKenzie vasoconstrictor assay in man are consistent with these results. The precise mechanisms of glucocorticoid action in asthma are unknown. Inflammation is recognized as an important component in the pathogenesis of asthma. Glucocorticoids have been shown to inhibit multiple cell types (e. g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and mediator production or secretion (e. g., histamine, eicosanoids, leukotrienes, and cytokines) involved in the asthmatic response. Text Continues Below
These anti-inflammatory actions of glucocorticoids may contribute to their efficacy in asthma. Though highly effective for the treatment of asthma, glucocorticoids do not affect asthma symptoms immediately. However, improvement following inhaled administration of fluticasone propionate can occur within 24 hours of beginning treatment, although maximum benefit may not be achieved for 1 to 2 weeks or longer after starting treatment. When glucocorticoids are discontinued, asthma stability may persist for several days or longer. Pharmacokinetics Absorption The activity of FLOVENT Inhalation Aerosol 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. Page: 1 | 2 | 3 | 4 | 5 | Next >>
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