Binding of glucocorticoids to human nasal tissue in vitro.
BACKGROUND
Intranasal application of glucocorticoids is an efficacious treatment of allergic rhinitis and some cases of nonallergic rhinitis. However, no data on binding of glucocorticoids to nasal tissue are available. Pronounced binding of the compound to the target tissue is favorable as it might serve as a local deposit delivering the glucocorticoid to specific receptors and it slows down the efflux of the compound into systemic circulation.


METHODS
Human nasal tissue was incubated with fluticasone propionate, budesonide, flunisolide and beclomethasone-17-monopropionate. Kinetics of binding and redistribution of the tissue-bound fraction into human plasma was monitored.


RESULTS
Binding of glucocorticoids to human nasal tissue was fast and highest for the lipophilic fluticasone propionate, followed by beclomethasone-17-monopropionate. Also, highest concentrations of these lipophilic glucocorticoids remained in nasal tissue after equilibration of drug-saturated tissue with plasma.


CONCLUSIONS
Lipophilic compounds exhibit a high tissue binding and retention which is an important property of topically applied glucocorticoids. It is the basis for prolonged action and low concentration of the compound in systemic circulation.
Esmailpour
N
N
Institute of Pharmaceutical Chemistry, Westfälische Wilhelms-Universität Münster, Germany.
Högger
P
P
Rohdewald
P
P
D000287:Administration, Topical; D000730:Androstadienes / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D018926:Anti-Allergic Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D018927:Anti-Asthmatic Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D001507:Beclomethasone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D019819:Budesonide / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009297:Nasal Mucosa / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism
D000730:Androstadienes; D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D005446:Fluocinolone Acetonide; D019819:Budesonide; C065857:beclomethasone 17-monopropionate; C007734:flunisolide; D000068298:Fluticasone; D001507:Beclomethasone