Response to inhaled albuterol during nocturnal asthma.
BACKGROUND
During conventional daytime studies of beta(2)-agonists, 1 puff of a metered-dose inhaler often produces a near maximum bronchodilator response. Consequently, the US Food and Drug Administration-approved dose of albuterol is only 1 to 2 puffs every 4 to 6 hours.


OBJECTIVE
To determine whether a higher dose of albuterol is required to normalize lung function during nocturnal asthma.


METHODS
Fifteen subjects (age, 18-37 years) were treated with albuterol metered-dose inhalers in a randomized crossover manner at the onset of nocturnal symptoms while sleeping in the Clinical Research Center and during the day when they were asymptomatic. The dose was doubled at 15-minute intervals to 16 cumulative puffs.


RESULTS
The mean +/- SD predose FEV(1) was lower at night than during the day (44% +/- 12% vs 68% +/- 9% predicted; P=.0001). The maximum FEV(1) achieved was also lower at night (84% +/- 15% vs 90% +/- 12%; P=.02). The nocturnal dose-response curve was shifted to the right. The median (25th, 75th percentiles) dose required to achieve 80% of the subject's personal best FEV(1) was substantially higher at night (5 [1, 19] vs 0.4 [<0.25, 2] puffs; P=.02), and the median time to achieve this endpoint was longer (47 [21, 90] vs 10 [0.2, 42] minutes; P=.005). No significant systemic effects were observed.


CONCLUSIONS
At night, the response was slower and required a higher dose because more severe airway obstruction was present on awakening. These results suggest that studies establishing the clinical dose of a beta(2)-agonist or assessing the equivalence of different formulations should be conducted in subjects with more severe reversible airway obstruction than is present during conventional daytime studies.
Hendeles
Leslie
L
College of Pharmacy and Pulmonology Division, Department of Pediatrics, University of Florida Health Sciences Center, PO Box 100486, 1600 SW Archer Road, Room MG-57, Gainesville, FL 32610-0486, USA. hendeles@cop.ufl.edu
Beaty
Russell
R
Ahrens
Richard
R
Stevens
Gary
G
Harman
Eloise M
EM
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D013997:Time Factors
D001993:Bronchodilator Agents; D000420:Albuterol