INHIBITION OF HISTAMINE-INDUCED SKIN WHEAL AND FLARE AFTER 5 DAYS OF MIZOLASTINE

Mizolastine is a new, nonsedating antihistamine providing satisfactory symptomatic relief in allergic rhinitis and urticaria. The purpose of this study was to use inhibition of wheal and flare formation after 2 -mu g intradermal histamine injections as a measure of the antihistami ne effect of repeated doses of mizolastine. Eight volunteers were enro lled in this four-arm, double-blind, cross-over, randomized study. Thr ee dose levels of once-daily mizolastine (5 mg, 10 mg, and 15 mg) were compared with placebo during 5-day dose periods. Histamine tests were performed before drug intake on days 1 and 5, and then 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours after drug intake on day 5. All 3 doses of m izolastine were more effective than placebo in suppressing wheal and f lare reactions, and the antihistamine activity was highest at both the 10- and 15-mg dose levels. The effect on the Pare reaction appeared w ithin 1 hour, reached a maximum effect 4 hours after administration, a nd persisted for as long as 24 hours. The relative changes in wheal an d flare areas were correlated with mizolastine trough plasma levels on day 5. Safety was satisfactory in all groups. This study confirms tha t mizolastine is a rapid and potent antihistamine; and its long-lastin g effectiveness indicates that a once-daily regimen is acceptable for clinical use.