TOPICAL AZELASTINE HAS A 12-HOUR DURATION OF ACTION AS ASSESSED BY HISTAMINE CHALLENGE-INDUCED EXUDATION OF ALPHA(2)-MACROGLOBULIN INTO HUMAN NASAL AIRWAYS

Background Oral anti-histamine drugs are widely used In the treatment of seasonal allergic rhinitis. Recently, anti-histamines have become a vailable also for topical treatment. Objective The present study, invo lving healthy subjects, examined the effect of topical azelastine on l uminal entry of alpha(2)-macroglobulin and symptoms evoked by repeat h istamine challenges during 24 h. The effect was compared to a clinical dose of the oral anti-histamine cetirizine and to placebo treatments. Methods Placebo and azelastine (0.254 mg per nasal cavity) were deliv ered as two consecutive actuations per nasal cavity using a nasal spra y device. Oral placebo and cetirizine (10 mg) were given as single dos es in a placebo-controlled (double-dummy), double-blind, and cross-ove r design. Histamine-challenges were given 1 h before treatment, and 1, 6, 9, 12, and 24 h after each treatment. The nasal mucosal surface wa s lavaged after each challenge. The lavage-fluid levels of alpha(2)-ma croglobulin were determined to assess mucosal exudation of bulk plasma , and nasal symptoms were scored. Results Histamine (40-400 mu g/mL) p roduced dose-dependent exudation and symptoms. Compared between each t reatment and placebo, azelastine and cetirizine reduced the 40 and/or 400 mu g/mL histamine-induced mucosal exudation of plasma from 1-12 h after treatment. In addition, cetirizine reduced the 40 mu g/mL histam ine-induced mucosal exudation of plasma 24 h after treatment. Differen ces between the two treatments were not evident regarding nasal sympto ms. Conclusion Histamine challenge-induced mucosal exudation of plasma appears to be a useful method for studies of the duration of action o f antihistamines, We conclude that topical azelastine is suited for b. i.d. therapy and that neither the exudative process nor watery secreti on may impede the efficacy or the duration of action of this nasal dru g.