Flusort Mechanism of Action

Pharmacology: Mechanism of Action: Fluticasone propionate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. Fluticasone propionate was 3-fold to 5-fold more potent than dexamethasone in assays.
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) ad mediators (eg, histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation. FLUTICASONE PROPIONATE 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 FLUTICASONE PROPIONATE 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 FLUTICASONE PROPIONATE Nasal Spray is due to the parent drug, fluticasone propionate. Indirect 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. Due to the low bioavailability by the intranasal route, the majority of pharmacokinetic data was obtained via other routes of administration.
Distribution: The volume of distribution averaged 4.2 L/kg following i.v administration. The percentage of fluticasone propionate bound to human plasma proteins averaged 91% with no obvious concentration relationship.
Metabolism: The total blood clearance of fluticasone propionate is high.
Elimination: Following intravenous dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of approximately 7.8 hours.
Special Populations: Fluticasone propionate nasal spray was not studied in any special populations, and no gender-specific pharmacokinetic data have been obtained.
Drug Interactions: Fluticasone propionate is a substrate of cytochrome P450 3A4. Caution should be exercised when other potent cytochrome P450 3A4 inhibitors are coadministered with fluticasone propionate.
Individualization of Dosage: Patients should use FLUTICASONE PROPIONATE Nasal Spray at regular intervals for optimal effect.