Dissolution in nasal fluid, retention and anti-inflammatory activity of fluticasone furoate in human nasal tissue ex vivo.

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.