title: Ketotifen inhibits the cutaneous but not the airway responses to platelet-activating factor in man.
abstract: We studied the effect of ketotifen, an oral antiallergic and antihistaminic drug, on the airway and cutaneous responses to platelet-activating factor (PAF) in a double-blind, randomized, and crossover study in six normal subjects. Ketotifen (three doses of 2 mg taken during a 14-hour period before PAF) did not alter PAF-induced bronchoconstriction and did not prevent the accompanying flushing and coughing. The transient neutropenia (74.5 +/- 4.8% fall; p less than 0.001) and rebound neutrophilia (104 +/- 55% rise) induced by PAF were not affected by ketotifen. On the day placebo was received, airway responsiveness to methacholine increased after PAF exposure with the concentration needed to cause a 40% fall in baseline partial expiratory flow rate (PC40), decreasing from 69.2 mg/ml (geometric standard error of the mean, 2.69) to 23.3 mg/ml (2.34) on day 3 (p less than 0.001). Ketotifen had no effect, because on the day ketotifen was administered, mean PC40 also decreased from 52.7 mg/ml (2.5) to 21.5 mg/ml (2.14) (p less than 0.01). In the skin, ketotifen reduced the flare area (from 8.05 +/- 3.60 to 1.14 +/- 0.29 cm2; p less than 0.05) and the wheal volume (from 0.068 +/- 0.010 to 0.045 +/- 0.008 cc; p = 0.02) induced by intradermal PAF (200 ng). Cutaneous responses to histamine (1 microgram) were significantly inhibited. Thus, the bronchoconstriction and bronchial hyperresponsiveness induced by PAF are not inhibited by ketotifen. Ketotifen inhibits PAF-induced wheal and flare in the skin, which is probably histamine dependent. The airway effects of PAF are unlikely to be mediated by histamine release.
authors.affiliation: Department of Thoracic Medicine, Brompton Hospital, London, England.
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
authors.forename: P
authors.initials: P
authors.lastname: Minette
authors.forename: M
authors.initials: M
authors.lastname: McCusker
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D000328:Adult; D000336:Aerosols; D001772:Blood Cell Count / Q000187:drug effects; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D006801:Humans; D007665:Ketotifen / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D010972:Platelet Activating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D011897:Random Allocation; D012882:Skin Tests
chemical_list: D000336:Aerosols; D008688:Methacholine Compounds; D010972:Platelet Activating Factor; D016210:Methacholine Chloride; D007665:Ketotifen