A review of the pharmacology and pharmacokinetics of inhaled fluticasone propionate and mometasone furoate

Background: Fluticasone propionate is an established corticosteroid adminis tered intranasally for the treatment of rhinitis or by oral inhalation for the treatment of asthma. Mometasone furoate, a closely related corticostero id currently available in an intranasal formulation, is being investigated in an oral inhalation formulation for the treatment of asthma. Objective: This article reviews available data on the comparative structure -activity relationships, chemistry, pharmacology, pharmacokinetics, and sys temic bioavailability of fluticasone propionate and mometasone furoate to a ssess whether claims of differences in the absolute systemic bioavailabilit y of the 2 compounds are supported by the published literature. Methods: Information for this review was identified through a MEDLINE searc h of the literature from 1966 to the present that contained the term mometa sone or fluticasone. The resulting list was narrowed by excluding articles dealing with dermatologic applications. A systematic review was conducted o f the identified literature pertaining to the molecular structure, topical potency, lipophilicity, pharmacokinetics, and bioavailability of the 2 agen ts. Additionally, the pharmacology of the 2 moieties was assessed by a revi ew of the available literature on receptor binding affinity, transactivatio n and transrepression potency, and inhibition of inflammatory-cell cytokine expression. Results: Based on the available data, fluticasone propionate and mometasone furoate have similar physicochemical properties and structure-activity rel ationships. When administered intranasally, mometasone furoate is reported to have comparable relative systemic bioavailability to that of fluticasone propionate (mean plasma area under the curve, 123 pmol.h/L vs 112 pmol.h/L , respectively). When administered as a single dose by dry powder inhaler, orally inhaled fluticasone propionate is reported to have a total systemic bioavailability of similar to 17%, whereas that of mometasone furoate is re ported to be <1%. However, the mometasone furoate bioavailability study tha t reported the latter value used lower drug doses and a less sensitive assa y than the fluticasone propionate bioavailability study. When multiple-dose data were used, mometasone furoate had an estimated 11% systemic bioavaila bility, similar to that of fluticasone propionate. Conclusions: Inhaled fluticasone propionate and mometasone furoate appear t o have comparable potential systemic absorption and, based on the total sys temic bioavailabilities of the parent compounds, have a low potential for s ystemic side effects at the recommended clinical doses. However, in the cas e of mometasone furoate, the contribution of the active metabolites to syst emic effects has not been adequately assessed.