Topical azelastine has a 12-hour duration of action as assessed by histamine challenge-induced exudation of α2-macroglobulin into human nasal airways


L. Greiff, Department of Otorhinolaryngology, Head and Neck Surgery, Lund University Hospital, S-221 85 Lund, Sweden.


Background Oral anti-histamine drugs are widely used in the treatment of seasonal allergic rhinitis. Recently, anti-histamines have become available also for topical treatment

Objective The present study, involving healthy subjects, examined the effect of topical azelastine on iuminal entry of α2-macroglobulin and symptoms evoked by repeat histamine challenges during 24 h. The effect was cotnpared 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 delivered as two consecutive actuations per nasal cavity using a nasal spray device. Oral placebo and cetirizine (10mg) were given as single doses in a placebo-controlled (double-dummy), double-blind, and cross-over design. Histamine-challenges were given 1 h before treatment, and 1, 6. 9, 12. and 24 h after each treatment. The nasal mucosal surface was lavaged after each challenge. The lavage-fiuid levels of α2-macroglobulin were determined to assess mucosal exudation of bulk plasma, and nasal symptoms were scored.

Results Histamine (40–400 μg/mL) produced dose-dependent exudation and symptoms. Compared between each treatment and placebo, azelastine and cetirizine reduced the 40 and/or 400μg/mL histamine-induced mucosal exudation of plasma from 1–12 h after treatment. In addition, cetirizine reduced the 40μg/mL histamine-induced mucosal exudation of plasma 24 h after treatment. Differences between the two treatments were not evident regarding nasal symptoms.

Conclusion Histamine challenge-induced mucosal exudation of plasma appears to be a useful method for studies of the duration of action of antihistamines. We conclude that topical azelastine is suited for b.i.d. therapy and that neither the exudative process nor watery secretion may impede the efficacy or the duration of action of tbis nasal drug.