A double-blind placebo controlled dose response study of noberastine on histamine induced weal and flare

The antihistaminic effects of 7 days treatment with each of three doses of noberastine (10, 20 and 30 mg) were compared to placebo in 12 healthy male volunteers. The antihistaminic activity was assessed from the inhibition of weal and flare formation after intradermal histamine injections. For both weal and flare there was a highly significant effect of treatment with each of the three doses of noberastine, compared to placebo. The 30 mg daily dose produced the maximum inhibition of weal and flare. The daily mean values for the assessment of sedation by visual analogue scales at 09.00 h, 15.00 h and 21.00 h showed no significant treatment, or order, effect for any of the three doses of noberastine compared to placebo. The mean steady-state plasma concentrations of noberastine were significantly higher with increasing daily doses of noberastine (trough concentrations: 1.0, 1.6 and 2.2 ng.ml-1; peak concentrations: 3.5, 13.4 and 20.9 ng.ml-1 for 10, 20 and 30 mg daily dose, respectively). The percentage weal inhibition correlated (r = 0.77) with steady-state noberastine plasma trough levels. The percentage flare inhibition showed a weaker correlation (r = 0.35) with steady-state noberastine plasma trough levels.