Pharmacokinetic/pharmacodynamic profile of mometasone furoate nasal spray: potential effects on clinical safety and efficacy

Abstract

Background: Mometasone furoate nasal spray (MFNS) is recommended as a first-line therapy for allergic rhinitis. The purpose of intranasal administration is to deliver maximally effective therapy to the affected nasal tissues while minimizing systemic exposure.

Objective: This article reviews the pharmacokinetic and pharmacodynamic properties of MFNS, highlighting the potential clinical relevance of data concerning its glucocorticoid receptor binding, bioavailability, and metabolism, and its role in activating and suppressing transcription of steroid-dependent genes.

Methods: A search of the MEDLINE and EMBASE databases (January 1995-July 2007) was undertaken to identify in vitro, preclinical, and clinical studies and review articles concerning MFNS. Searches were also conducted to identify articles on the pharmacokinetics, pharmacodynamics, and adverse effects of the intranasal corticosteroids discussed in this article. Pertinent abstracts from allergy society meetings and data from the author's research experience were also included.

Results: The data reviewed indicate that MFNS has a number of qualities that are important in achieving nasal selectivity with minimal systemic adverse effects. For example, MFNS is stable in nasal tissues and is efficiently metabolized in the liver (AUC for a 400-microg dose: 127 fmol/mL x h). Its systemic bioavailability (0.46%) is one of the lowest among currently available intranasal corticosteroids. Bioactive glucocorticoid metabolites have not been observed in humans. The results of immunologic studies suggest that MFNS may reverse the exaggerated T-helper cell type 2 (Th2)-related cytokine response seen in allergic disease through preferential inhibition of Th2 over the T-helper cell type 1-related cytokine.

Conclusions: MFNS is an intranasal corticosteroid with a low potential for systemic adverse effects. The efficacy and safety profiles of MFNS seen in clinical use are consistent with its pharmacokinetic and pharmacodynamic properties.