The 24 h duration of bronchodilator action of the salmeterol/fluticasone combination inhaler.
BACKGROUND
The duration of bronchodilator action of the long-acting beta agonist salmeterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of salmeterol, administered from the combination salmeterol/fluticasone (SFC) Accuhaler significantly attenuates the circadian rhythm in airway tone over 24 h.


METHODS
Eighteen subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, double dummy, placebo controlled, cross-over study. Subjects inhaled, in random order, placebo, salbutamol (200 microg) or SFC (50/100 microg) administered in the evening (2000 h) on three separate occasions. Lung function measurements including FEV1, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity (MEF(25-75%)) were assessed at baseline, at 1 h and subsequently every 4 h post-dose for 24 h.


RESULTS
Compared with placebo, SFC significantly improved the three measures of airways function throughout the 24 h period, with a difference in FEV1 at 24 h of 0.24 l (0.00-0.47 l). SFC abolished the biphasic pattern of the circadian rhythm in airway tone. In contrast, salbutamol had a significant bronchodilator action of 4-8 h, depending on the lung function parameter measured.


CONCLUSIONS
The single evening administration of SFC via the Accuhaler resulted in a duration of bronchodilation of at least 24 h, with the abolition of the accentuated biphasic circadian variation in airway tone observed in asthma.
Masoli
Matthew
M
Medical Research Institute of New Zealand, 3rd Floor, 99 The Terrace, PO Box 10055, Wellington 6001, New Zealand.
Weatherall
Mark
M
Ayling
Joanne
J
Williams
Mathew
M
Beasley
Richard
R
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002940:Circadian Rhythm; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004812:Epidemiologic Methods; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D000068299:Salmeterol Xinafoate
D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol