Onset and duration of action of levocabastine nasal spray in atopic patients under nasal challenge conditions

Background: Although prior studies have documented the rapid onset of actio n of topical intranasal levocabastine (LEV), little is known about its dura tion of action under nasal challenge conditions. Objectives: We sought to assess the onset and duration of action of escalat ing doses of LEV nasal spray by using a nasal allergen challenge (NAC) mode l. Methods: Eighteen asymptomatic subjects with histories of seasonal allergic rhinitis were enrolled into a randomized, single-blind, placebo-controlled , dose-ranging crossover study. Each patient was randomly assigned to recei ve single doses of placebo and intranasal LEV 0.1, 0.2, and 0.4 mg during 2 parts of the study. In part 1 (onset of action), NAC consisted of a single dose of allergen administered 5 minutes after study drug treatment. In par t 2 (duration of action), NAC consisted of increasing doses of allergen adm inistered 0.5, 6, 12, and 24 hours on separate days after study drug treatm ent. Nasal symptom scores (NSSs) and nasal peak expiratory pow rates were m easured after NAC in both phases of the study, Blood samples for plasma LEV concentrations were drawn after each NAC. Results: In part 1, NSSs were significantly lower after the administration of LEV 0.1, 0.2, and 0.4 mg compared with placebo (P < .05). In part 2, NSS s were significantly tower after LEV doses of 0.2 and 0.4 mg compared with placebo at 0.5, 6, 12, and 24 hours after treatment (P < .05), The mean pro vocative dose of allergen required to elicit a positive nasal reaction was increased after LEV doses of 0.2 and 0.4 mg at 0.5, 6, and 12 hours after t reatment. Nasal peak expiratory flow rates demonstrated no significant diff erences between LEV and placebo for any doses at any time points. Mean plas ma LEV concentrations were low (range, 0 to 3.7 ng/mL) after all doses and did not correlate with drug efficacy. Conclusions: Single intranasal LEV doses of 0.1, 0.2, and 0.4 mg significan tly reduced the severity of the immediate nasal response to allergen when a dministered 5 minutes before NAC. This protective effect against NAC contin ued to be present 24 hours after administration of LEV doses of 0.2 and 0.4 mg. Efficacy in blocking the reaction to NAC did not correlate with plasma LEV levels, suggesting that the inhibitory effect was due largely to topic al rather than systemic effects.