Central and peripheral evaluation of rupatadine, a new antihistamine/platelet-activating factor antagonist, at different doses in healthy volunteers

Aims: To assess peripheral anti-H-1 and central nervous system (CNS) activity of single increasing doses of rupatidine fumarate (RU), a new antihistamine/platelet-activating factor antagonist compound, in comparison with hydroxyzine and placebo. Methods: Eighteen healthy young subjects of both sexes took part in a crossover, randomised, double-blind, placebo-controlled study. Treatments tested were: RU 10, 20, 40 and 80 mg and hydroxyzine 25 mg, as a positive standard. Before and several times after drug intake, peripheral anti-H-1 activity was appraised by the skin reactivity to intradermal injection of histamine. CNS effects were also obtained by objective tests of psychomotor performance and subjective mood scales. Results: All active treatments showed a significant reduction of the wheal and flare reaction in relation to placebo, RU displaying a potent dose-dependent inhibition pattern. The global nonparametric Friedman test to changes from placebo in 15 objective variables from psychomotor performance showed a significant impairment of similar magnitude after hydroxyzine 25 mg (p = 0.01) and RU 80 mg (p = 0.02), but this was slower in development and recovery after the latter. After RU 40 mg, a smaller impairment was also obtained (p = 0.04). Activity (p = 0.01) and drowsiness (p = 0.02) scales showed significant changes, the subjects feeling less active and more drowsy after all active treatments. Conclusion: RU presents a potent dose-dependent peripheral anti-H-1 activity, displaying psychomotor impairment activity only at the highest dose (80 mg), while therapeutically relevant lower doses (10 and 20 mg) were similar to placebo. Copyright (C) 2004 S. Karger AG, Basel.