Bronchodilator subsensitivity to salbutamol after twice daily salmeterol in asthmatic patients.
In view of current concerns about use of regular beta-2 agonists, and the place of the newer long-acting drugs, we decided to evaluate whether continuous exposure to twice daily salmeterol results in a blunting of the acute bronchodilator response to repeated doses of salbutamol, as might be administered in the management of an acute asthma attack. After a 2 week run-in without beta-2 agonists, 17 asthmatic patients (mean [SE] age 34 [3] years, mean forced expiratory volume in 1 s [FEV1] 64 [2.7]% of predicted) were randomised to receive salmeterol 50 micrograms twice daily or placebo for 4 weeks in a double-blind cross-over fashion. A histamine challenge test was done 12 h after the last dose of each treatment period, and dose-response curves to inhaled salbutamol (200-3200 micrograms) were constructed 36 h after the last dose. Patients treated with salmeterol had reduced bronchodilator responses to salbutamol in terms of FEV1 and peak expiratory flow rate (PEFR) than those treated with placebo. The reduction in response equated with a 2.5-fold and a fourfold greater dose of salbutamol being required to produce a given FEV1 and PEFR, respectively. There was a significant reduction in lymphocyte beta-2 adrenoceptor density after salmeterol compared with placebo and run-in. Salmeterol remained effective in terms of disease control, with a significant improvement in morning PEFR compared with placebo that was maintained over the 4 week treatment period.(ABSTRACT TRUNCATED AT 250 WORDS)
Grove
A
A
Department of Clinical Pharmacology, Ninewells Hospital, University of Dundee, UK.
Lipworth
B J
BJ
D000208:Acute Disease; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009330:Nebulizers and Vaporizers; D010366:Peak Expiratory Flow Rate; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000068299:Salmeterol Xinafoate; D006632:Histamine; D000420:Albuterol