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

• Published in: Clinical therapeutics Vol. 23; no. 9; pp. 1339 - 1354
• Main Authors: Crim, Courtney, Pierre, Lisa N., Daley-Yates, Peter T.
• Format: Journal Article
• Language: English
• Published: Belle Mead, NJ EM Inc USA 01.09.2001; Excerpta Medica
• Subjects: Administration, Intranasal; Androstadienes - administration & dosage; Androstadienes - pharmacology; Biological and medical sciences; Biological Availability; Cytokines - drug effects; Fluticasone; fluticasone propionate; Humans; Medical sciences; Mometasone Furoate; Pharmacology. Drug treatments; Pregnadienediols - administration & dosage; Pregnadienediols - pharmacology; Receptors, Glucocorticoid - drug effects; Respiratory system; Rhinitis, Allergic, Perennial - drug therapy; structure-activity relationship; Time Factors; total systemic bioavailability; total systemic bioavailability; mometasone furoate; structure-activity relationship; fluticasone propionate; Human; Corticosteroid; Review; Bioavailability; Fluticasone; Antiasthma agent; In vitro; Mometasone; Inhalation; In vivo; Structure activity relation; Pharmacokinetics; Comparative study; Physicochemical properties
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(01)80113-2

Background: Fluticasone propionate is an established corticosteroid administered intranasally for the treatment of rhinitis or by oral inhalation for the treatment of asthma. Mometasone furoate, a closely related corticosteroid 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 systemic bioavailability of fluticasone propionate and mometasone furoate to assess whether claims of differences in the absolute systemic bioavailability of the 2 compounds are supported by the published literature. Methods: Information for this review was identified through a MEDLINE search of the literature from 1966 to the present that contained the term mometasone or fluticasone. The resulting list was narrowed by excluding articles dealing with dermatologic applications. A systematic review was conducted of the identified literature pertaining to the molecular structure, topical potency, lipophilicity, pharmacokinetics, and bioavailability of the 2 agents. Additionally, the pharmacology of the 2 moieties was assessed by a review of the available literature on receptor binding affinity, transactivation 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 relationships. 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 ∼17%, whereas that of mometasone furoate is reported to be <1%. However, the mometasone furoate bioavailability study that reported the latter value used lower drug doses and a less sensitive assay than the fluticasone propionate bioavailability study. When multiple-dose data were used, mometasone furoate had an estimated 11% systemic bioavailability, similar to that of fluticasone propionate. Conclusions: Inhaled fluticasone propionate and mometasone furoate appear to have comparable potential systemic absorption and, based on the total systemic bioavailabilities of the parent compounds, have a low potential for systemic side effects at the recommended clinical doses. However, in the case of mometasone furoate, the contribution of the active metabolites to systemic effects has not been adequately assessed.