Flonase

[Fluticasone]

Clinical Pharmacology
CLINICAL PHARMACOLOGY

Mechanism of Action

Fluticasone propionate is a synthetic, trifluorinated corticosteroid with anti-inflammatory activity. In vitro dose response studies on a cloned human glucocorticoid receptor system involving binding and gene expression afforded 50% responses at 1.25 and 0.17 nM concentrations, respectively. Fluticasone propionate was 3-fold to 5-fold more potent than dexamethasone in these assays. Data from the McKenzie vasoconstrictor assay in man also support its potent glucocorticoid activity.

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In preclinical studies, fluticasone propionate revealed progesterone-like activity similar to the natural hormone. However, the clinical significance of these findings in relation to the low plasma levels (see Pharmacokinetics) is not known. The precise mechanism through which fluticasone propionate affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e. g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e. g., histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation.

In 7 trials in adults, FLONASE Nasal Spray has decreased nasal mucosal eosinophils in 66% (35% for placebo) of patients and basophils in 39% (28% for placebo) of patients. The direct relationship of these findings to long-term symptom relief is not known.

FLONASE Nasal Spray, like other corticosteroids, is an agent that does not have an immediate effect on allergic symptoms. A decrease in nasal symptoms has been noted in some patients 12 hours after initial treatment with FLONASE Nasal Spray. Maximum benefit may not be reached for several days. Similarly, when corticosteroids are discontinued, symptoms may not return for several days.

Pharmacokinetics

Absorption

The activity of FLONASE Nasal Spray is due to the parent drug, fluticasone propionate. Indirect calculations indicate that fluticasone propionate delivered by the intranasal route has an absolute bioavailability averaging less than 2%. After intranasal treatment of patients with allergic rhinitis for 3 weeks, fluticasone propionate plasma concentrations were above the level of detection (50 pg/ mL) only when recommended doses were exceeded and then only in occasional samples at low plasma levels.

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