The in vivo potency and selectivity of azelastine as an H1 histamine-receptor antagonist in human airways and skin.

Azelastine is a novel histamine H1 antagonist with putative antileukotriene activity in guinea pigs. With three different doses of oral azelastine, we have performed a dose-response study to determine its protective effect on the airways against histamine-induced bronchoconstriction in 12 patients with mild, atopic asthma. On 4 separate days, patients undertook standardized inhalation-challenge tests with increasing concentrations of histamine (0.03 to 32 mg/ml) 4 hours after placebo or azelastine, 4.4, 8.8, and 17.6 mg, administered double blind and in random order. On 2 additional days, patients underwent methacholine challenge tests after placebo or azelastine, 17.6 mg. Baseline FEV1 between treatment days and 4 hours after placebo and azelastine did not change significantly. The three doses of azelastine, 4.4, 8.8, and 17.6 mg, increased the concentration of histamine required to cause a 20% fall in FEV1 (PC20) from 0.16 mg/ml geometric mean (GM) after placebo to 1.98 (p less than 0.01), 8.8 (p less than 0.01), and 8.1 (p less than 0.01) mg/ml, respectively. GM potency ratios derived from the PC20 values obtained for each patient indicated that the three increasing doses of azelastine displaced the histamine dose-response curve to the right by factors of 12.8, 54.4, and 50.2. Azelastine had no effect on the airway response to methacholine with GM PC20 values of 0.16 and 0.19 after placebo and azelastine, 17.6 mg. Azelastine is a potent H1 histamine-receptor antagonist on human airways in vivo without demonstrable anticholinergic effect.