Dissolution in nasal fluid, retention and anti-inflammatory activity of fluticasone furoate in human nasal tissue ex vivo
Article first published online: 17 JUN 2009
© 2009 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 39, Issue 10, pages 1540–1550, October 2009
How to Cite
Baumann, D., Bachert, C. and Högger, P. (2009), Dissolution in nasal fluid, retention and anti-inflammatory activity of fluticasone furoate in human nasal tissue ex vivo. Clinical & Experimental Allergy, 39: 1540–1550. doi: 10.1111/j.1365-2222.2009.03306.x
- Issue published online: 10 SEP 2009
- Article first published online: 17 JUN 2009
- Submitted 12 January 2009; revised 7 May 2009; accepted 11 May 2009
- human nasal tissue;
Background Intranasal glucocorticoids represent the most effective pharmacologic treatment of allergic rhinitis. So far, no clinical data are available that compare fluticasone furoate (FF) with other intranasally applied glucocorticoids.
Objective Because the pharmacokinetic behaviour of drugs governs their presence at the therapeutic target site we analysed selected in vitro properties of FF in comparison with triamcinolone acetonide (TCA), budesonide (Bud), fluticasone propionate (FP) and mometasone furoate (MF). Additionally, we determined the anti-inflammatory activity of the glucocorticoid fraction residing in human nasal tissue samples after washing.
Methods We analysed the solubility of the compounds in artificial human nasal fluid and the retention in human nasal tissue as well as typical spray volumes of commercially available drug preparations. As an anti-inflammatory measure, we evaluated the inhibition of IL-8 release from epithelial cells.
Results FF is delivered in the smallest application volume per spray. Despite the low aqueous solubility of glucocorticoids, a fraction of the compounds is already dissolved in the aqueous supernatants of drug preparations (Bud>TCA>FP>MF>FF). The dissolution of FP, MF and FF was significantly enhanced in artificial nasal fluid and FF displayed the most pronounced enhancement of solubility in the presence of proteins. Consistent with this result, the highest retention in nasal tissue was observed for FF, followed by FP>MF>Bud>TCA. After washing of the nasal tissue samples, all compounds inhibited IL-8 release, with FF displaying the highest activity.
Conclusion FF displayed beneficial properties for nasal application. Its low application volume per spray is a prerequisite for effective drug utilization by avoiding immediate loss by nose runoff or drip down the throat. Sustained dissolution and high tissue binding of FF should contribute towards an extended presence of compounds in nasal tissue as a basis for a prolonged pharmacologic activity.