title: The effect of ketotifen on bronchial beta-adrenergic tachyphylaxis in normal human volunteers.
abstract: The effect of ketotifen on bronchial beta-adrenergic tachyphylaxis was studied in healthy volunteers. In a 2-week pilot study, 19 volunteers inhaled 300 micrograms of salbutamol, four times a day. Ten subjects became tachyphylactic to inhaled salbutamol, assessed by a dose-response curve, before and after the 2 weeks of treatment from a metered-dose inhaler. These 10 subjects were then involved in a double-blind, crossover study comparing the effect of ketotifen, 1 mg in the evening during 1 week, and 1 mg, twice daily, during 3 weeks, and placebo on the bronchial beta-adrenergic tachyphylaxis induced by the concomitant administration during the last 2 weeks of each treatment period of 300 micrograms of salbutamol, four times a day, from a metered-dose inhaler. The end of the pilot study preceded the double-blind study by at least 1 month. However, the salbutamol dose-response curve at the beginning of the double-blind study was still significantly decreased, compared to the dose-response curve before the pilot study. During placebo treatment, a further decrease in bronchial beta-adrenergic sensitivity was observed. Treatment with ketotifen prevented the induction of further beta-adrenergic tachyphylaxis. Each 2 weeks of treatment with inhaled salbutamol increased significantly the baseline specific airway conductance; therefore, based on the present data, it is impossible to determine whether ketotifen also restores the sensitivity of an already desensitized beta-adrenergic system in the airways.
authors.affiliation: Department of Respiratory Diseases, University Hospital, Ghent, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: M
authors.initials: M
authors.lastname: Van der Straeten
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage; D001980:Bronchi / Q000187:drug effects / Q000276:immunology*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007665:Ketotifen / Q000494:pharmacology*; D008297:Male; D010919:Placebos; D011897:Random Allocation; D013564:Sympathetic Nervous System / Q000187:drug effects; D013618:Tachyphylaxis
chemical_list: D010919:Placebos; D000420:Albuterol; D007665:Ketotifen