title: Allergen-induced increase in airway responsiveness is not inhibited by acute treatment with ketotifen or clemastine.
abstract: Allergen-induced increase in airway responsiveness to histamine or methacholine provides a useful model for investigation of prophylactic or "antiinflammatory" asthma treatments. This can be inhibited by corticosteroids or by sodium cromoglycate but not by beta agonists or by theophylline. A single-blind, crossover, random-order trial was conducted to compare ketotifen, clemastine, and placebo in six atopic subjects undergoing allergen inhalation tests. Ketotifen, 2 mg; clemastine, 1 mg; and placebo one tablet were administered twice daily for four days (eight doses) up to and including one hour before allergen inhalation. None of the three produced a significant reduction in the allergen-induced early or late asthmatic responses, or in the allergen-induced fall in methacholine PC20. There was a subtle nonsignificant suggestion of a reduction in the early portion of the early asthmatic response induced by both ketotifen and clemastine. Both ketotifen and clemastine produced a similar 8-fold inhibition of histamine skin test endpoint indicating equal systemic H1 blocking effect at the time of allergen inhalation. Sodium cromoglycate, 10 mg, single dose, by metered dose inhaler ten minutes before allergen challenge, added as an unblinded "positive control", inhibitory effects on the allergen-induced late and presumed inflammatory sequelae. It is possible that longer treatment periods (several weeks or months) might prove effective.
authors.affiliation: Department of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada.
authors.forename: D W
authors.initials: DW
authors.lastname: Cockcroft
authors.forename: M
authors.initials: M
authors.lastname: Keshmiri
authors.forename: K Y
authors.initials: KY
authors.lastname: Murdock
authors.forename: B C
authors.initials: BC
authors.lastname: Gore
mesh_terms: D000328:Adult; D000403:Airway Resistance / Q000187:drug effects* / Q000502:physiology; D000485:Allergens / Q000502:physiology*; D000704:Analysis of Variance; D001249:Asthma / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D002974:Clemastine / Q000592:standards / Q000627:therapeutic use*; D004205:Cromolyn Sodium / Q000592:standards / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000032:analysis; D006801:Humans; D007665:Ketotifen / Q000592:standards / Q000627:therapeutic use*; D008297:Male; D012882:Skin Tests
chemical_list: D000485:Allergens; D006632:Histamine; D002974:Clemastine; D004205:Cromolyn Sodium; D007665:Ketotifen