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 action of topical intranasal levocabastine (LEV), little is known about its duration of action under nasal challenge conditions.


OBJECTIVE
We sought to assess the onset and duration of action of escalating doses of LEV nasal spray by using a nasal allergen challenge (NAC) model.


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 receive 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 part 2 (duration of action), NAC consisted of increasing doses of allergen administered 0.5, 6, 12, and 24 hours on separate days after study drug treatment. Nasal symptom scores (NSSs) and nasal peak expiratory flow rates were measured 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, NSSs were significantly lower 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 provocative 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 treatment. Nasal peak expiratory flow rates demonstrated no significant differences between LEV and placebo for any doses at any time points. Mean plasma 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 significantly reduced the severity of the immediate nasal response to allergen when administered 5 minutes before NAC. This protective effect against NAC continued 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 topical rather than systemic effects.
Corren
J
J
Allergy Research Foundation, Inc, Los Angeles, CA 90025, USA.
Rachelefsky
G
G
Spector
S
S
Schanker
H
H
Siegel
S
S
Holton
D
D
Karcher
K
K
Travers
S
S
D000281:Administration, Intranasal; D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009299:Nasal Provocation Tests; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006109:Poaceae / Q000009:adverse effects; D011058:Pollen / Q000009:adverse effects / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000378:metabolism; D012720:Severity of Illness Index; D016037:Single-Blind Method; D014197:Trees / Q000009:adverse effects
D000485:Allergens; D006634:Histamine H1 Antagonists; D010880:Piperidines; C047340:levocabastine