title: Clinical efficacy and pharmacokinetic profiles of intranasal and oral cetirizine in a repeated allergen challenge model of allergic rhinitis.
abstract: BACKGROUND
  Intranasal and oral antihistamines are effective in treating allergic rhinitis. Studies comparing these routes of administration of an antihistamine regarding efficacy and pharmacokinetic profile are lacking.
  
  
  OBJECTIVE
  To compare topical and oral routes of administration of cetirizine regarding efficacy, plasma exudation, and systemic drug levels in a repeated allergen challenge model of allergic rhinitis.
  
  
  METHODS
  Oral cetirizine dihydrochloride, 10 mg once daily, and topical cetirizine dinitrate in a dose corresponding to 4.4 mg of the dihydrochloride salt twice daily were given to grass pollen-sensitive individuals for 12 days in a double-blind, placebo-controlled, crossover design. Timothy grass pollen allergen challenges were given once daily for 7 days using a nasal spray device. Nasal symptoms and peak inspiratory flow were recorded in the morning, 10 minutes after allergen challenge, and in the evening. The pharmacokinetics of the treatments was monitored in 8 patients. The remaining 28 patients were challenged topically with histamine 12 and 24 hours after the final topical and oral cetirizine doses, respectively. Nasal lavage levels of alpha2-macroglobulin were determined to evaluate histamine-induced mucosal plasma exudation.
  
  
  RESULTS
  During the last 3 days of the repeated allergen challenge model, chronic symptoms were established. Both treatments reduced symptoms 10 minutes after allergen challenge (P < .001 vs placebo). Neither treatment reduced morning and evening symptoms or nasal peak inspiratory flow. Topical, but not oral, cetirizine reduced histamine-induced plasma exudation (P < .01 vs placebo) when systemic drug levels were similar in the 2 treatment regimens.
  
  
  CONCLUSIONS
  Topical and oral cetirizine reduced acute nasal symptoms produced by allergen challenges in patients with established chronic symptoms. There were also antihistaminic effects of topical cetirizine not related to systemic drug levels.
authors: Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden. Magnus.Korsgren@med.lu.se
authors: Magnus
authors: M
authors: Korsgren
authors: Morgan
authors: M
authors: Andersson
authors: Olof
authors: O
authors: Borgå
authors: Lars
authors: L
authors: Larsson
authors: Marie
authors: M
authors: Aldén-Raboisson
authors: Ulf
authors: U
authors: Malmqvist
authors: Lennart
authors: L
authors: Greiff
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000485:Allergens; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D017332:Cetirizine / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D009299:Nasal Provocation Tests; D011058:Pollen; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D018926:Anti-Allergic Agents; D039563:Histamine H1 Antagonists, Non-Sedating; D017332:Cetirizine