A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis,☆☆,

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Abstract

The anti-inflammatory activity of corticosteroids has prompted the exploration of their use in the treatment of allergic rhinitis. The development of intranasal steroids has resulted in several agents with quick actions, localized effects, and great efficacy in the treatment of seasonal allergic rhinitis and the prophylactic management of perennial rhinitis. This article presents a concise review of the preclinical and clinical evidence with these new agents and provides data-based guidance for the selection of optimal agents. The survey reveals that mometasone furoate, a new inhaled steroid with topical activity, has the greatest binding affinity for the glucocorticoid receptor, followed by fluticasone propionate, budesonide, triamcinolone acetonide, and dexamethasone. Mometasone furoate also has strong anti-inflammatory activity, with IL-4 and IL-5 inhibition activities equivalent to those of fluticasone propionate. Clinically, both mometasone furoate and fluticasone propionate appear to be well tolerated, to have quick onsets of action, and to be equivalent in efficacy in the treatment of seasonal allergic and perennial rhinitis. Of the intranasal steroids currently available, mometasone furoate has been shown to have the least systemic availability and, consequently, is expected to have the fewest systemic side effects. Some suppression of overnight cortisol levels has been reported with fluticasone propionate (indicative of hypothalamic-pituitary-adrenal axis suppression). (J Allergy Clin Immunol 1999;104:150-8.)

Section snippets

THE NEWER INTRANASAL STEROIDS: PRECLINICAL DATA

The anti-inflammatory effects of glucocorticoids are specific receptor-mediated actions inherently dependent on the binding of the steroid drug with intracellular glucocorticoid receptors (GR) and subsequent transcriptional activation leading to target-gene expression. The effects of glucocorticoids are thus dependent on their respective receptor-binding affinities and postbinding transcriptional activities. These parameters can be studied in vitro, and the relative in vivo potencies of agents

THE NEWER INTRANASAL STEROIDS: CLINICAL DATA

The actions of intranasal steroids seen in preclinical studies clarified somewhat the utility and mechanism of action of these agents in allergic inflammatory diseases. The in vitro tests were also a useful means of predicting and comparing the actions of the many drugs in this class. However, various other factors, such as metabolism, systemic availabilities, and formulation effects, may alter the predicted rank order of potencies in vivo. Allergen challenge tests and clinical trials with

CORTICOSTEROID SELECTION: PHARMACOKINETIC AND PHARMACODYNAMIC BEARINGS

It is clear from the preceding sections that topical glucocorticoids act by specific receptors to inhibit various inflammatory actions in both the immediate and subsequent time points after allergen exposure. Although the anti-inflammatory actions of these agents have been graded in vitro and confirmed in various clinical assays, in the final analysis agent efficacy, potency, usage, and compliance will depend on several factors, including the onset of action, ratio of systemic to local effects,

CONCLUSION

The development of new intranasal steroids has been based on scientific reasoning and chemical reconfiguration. Thus newer corticosteroids are more lipophilic, have greater affinities for GRs, and are more readily and completely metabolized by the liver, allowing for quick-acting drugs with generally localized actions and rapid elimination. Here we have compared the most commonly used intranasal corticosteroid agents through a review of their preclinical and clinical testing data (Table IV).1, 3

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    Supported by an unrestricted educational grant from Schering/Key Pharmaceuticals, Schering Corporation.

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    Reprint requests: William R. Lumry, MD, American Board of Allergy and Immunology, 9900 N Central, Suite 525, Dallas, TX 75231.

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