Dose-related protection against histamine-induced bronchoconstriction by inhaled salmeterol.
A double-blind crossover study was carried out in 8 subjects to compare the effect of inhaled salmeterol 12.5, 50 and 100 micrograms with inhaled salbutamol 200 micrograms on resting lung function and on bronchoconstriction in response to inhaled histamine up to 12 hours following each treatment. Changes in resting lung function were measured using forced expiratory volume in one second (FEV1) and flow at 70% of vital capacity taken from partial expiratory flow volume curves (pEFR70). The concentrations of histamine which produced a 15% fall in FEV1 (PC15) and a 40% fall in pEFR70 (PC40) were also measured. The peak bronchodilator effect after salmeterol 50 and 100 micrograms was similar in magnitude to salbutamol 200 micrograms. Salmeterol produced dose-related changes in lung function and protection against histamine-induced bronchoconstriction. The duration of the effect of salmeterol (50 and 100 micrograms) was longer than that for salbutamol (200 micrograms). Although pEFR70 is a more sensitive measure of lung function there was no greater separation between different doses of salmeterol than with FEV1. Both salmeterol and salbutamol were well tolerated.
Department of Clinical Pharmacology, Glaxo Research and Development Limited, Greenford, Middlesex, UK.
J G
JG
Maconochie
L H
LH
Denyer
H
H
Hassani
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008448:Maximal Expiratory Flow Rate / Q000187:drug effects; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D006632:Histamine; D000420:Albuterol