title: Formoterol thrice weekly does not result in the development of tolerance to bronchoprotection.
abstract: BACKGROUND
  Loss of bronchoprotection routinely follows regular treatment with beta2-agonists. There are no data on the effects on bronchoprotection for thrice weekly use of a beta2-agonist.
  
  
  METHODS
  A double-blind, randomized, placebo controlled crossover trial was conducted to investigate the effects of thrice weekly administration of 12 microg of formoterol versus placebo on bronchoprotection against methacholine. As an expected positive control, formoterol 12 microg once daily was also evaluated.
  
  
  RESULTS
  There was no significant difference versus placebo in the bronchoprotective effects of 12 microg of formoterol administered on day 8, following daily treatment for seven days or treatment every other day (analysis of variance P=0.34). However, a nonsignificant trend towards lower concentration of methacholine that caused a 20% fall in forced expiratory volume in 1 s developed only following the daily formoterol dosing.
  
  
  CONCLUSIONS
  Thrice weekly dosing does not result in the development of tolerance to bronchoprotection against the direct acting stimulus methacholine.
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Royal University Hospital, Saskatoon, Saskatchewan.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Davis
authors.forename: John K
authors.initials: JK
authors.lastname: Reid
authors.forename: Donald W
authors.initials: DW
authors.lastname: Cockcroft
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D001249:Asthma / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068759:Formoterol Fumarate