Relative receptor affinity comparisons among inhaled/intranasal corticosteroids: perspectives on clinical relevance

Background: Pharmacokinetic properties, dosing regimen, and potency at the site of action are among the factors that influence activity of a corticosteroid. The potency of a corticosteroid at the site of action is determined significantly by its affinity to the glucocorticoid receptor. Recent literature on topical corticosteroids reveals an increasing emphasis on comparative relative receptor affinity values as a key method of differentiating among various corticosteroid compounds, particularly with regard to clinical efficacy. Methods: A response was formulated to: Valotis A, Högger P: Human receptor kinetics and lung tissue retention of the enhanced-affinity glucocorticoid fluticasone furoate. Respir Res 2007, 8:54. Results: Relative receptor binding affinities, while often showing significant variability across different laboratories, are a valid parameter when a comparison of the pharmacological activity of various glucocorticoids at the site of action is desired. Unfortunately within this context, scientific literature including the article from Valotis and Högger, confuse differences in potency (concentration or dose necessary to achieve a certain effect) with differences in efficacy (a quantitative difference in the overall maximum effect, even if all the receptors are occupied). All glucocorticoids will show the same efficacy as long as the selected dose will occupy the same number of receptors. Conclusion: While relative receptor affinities are useful for comparing in vitro potencies of corticosteroids, these data are not representative of physiologic conditions and should not be used as a basis for comparing the presumed effectiveness of compounds in a clinical situation. Topical corticosteroids, such as beclomethasone dipropionate, budesonide, triamcinolone acetonide, flunisolide, ciclesonide, mometasone furoate (MF), fluticasone propionate (FP), and fluticasone furoate (FF) are first-line treatments for upper respiratory allergic conditions such as asthma and seasonal/perennial rhinitis, as they provide local efficacy and, thereby, reduce systemic glucocorticoid exposure [1-4]. In recent literature, comparative relative receptor affinity (RRA) values for glucocorticoid receptors in nasal/lung tissue are increasingly used to differentiate among topical corticosteroids. In many instances, the presentation of RRA data and rank ordering of compounds is accompanied by overt or subtle implications of clinical efficacy ramifications. While RRA has a rightful place in the comparison of in vitro potency of corticosteroids, practicing clinicians need to understand the limitaPublished: 24 November 2008 Respiratory Research 2008, 9:75 doi:10.1186/1465-9921-9-75 Received: 16 May 2008 Accepted: 24 November 2008 This article is available from: http://respiratory-research.com/content/9/1/75 © 2008 Hochhaus; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.