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 available also for topical treatment.

OBJECTIVE

The present study, involving healthy subjects, examined the effect of topical azelastine on luminal entry of alpha 2-macroglobulin and symptoms evoked by repeat histamine 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 delivered as two consecutive actuations per nasal cavity using a nasal spray device. Oral placebo and cetirizine (10 mg) 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-fluid levels of alpha 2-macroglobulin were determined to assess mucosal exudation of bulk plasma, and nasal symptoms were scored.

RESULTS

Histamine (40-400 micrograms/mL) produced dose-dependent exudation and symptoms. Compared between each treatment and placebo, azelastine and cetirizine reduced the 40 and/or 400 micrograms/mL histamine-induced mucosal exudation of plasma from 1-12 h after treatment. In addition, cetirizine reduced the 40 micrograms/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 this nasal drug.