Cumulative and single-dose design to assess the bronchodilator effects of β2-agonists in individuals with asthma

dWith the development of different chlorofluorocarbon (CFC)-free metered dose aerosol and dry powder devices, it is necessary to study and validate the methods used for assessing and comparing their efficacy. This study evaluated the cumulative dose design by determining the bronchodilator response to salbutamol given according to either a high or a low cumulative dose regimen. Adults with asthma (n = 24) were studied in a placebo-controlled, randomized, double-blind, cross-over design. On separate days, cumulative doses of salbutamol (50+50+100+200 or 100+100+200+400 or 400+0+0+0 or 0+0+0+0 mug) were given via Turbuhaler with 30 min between doses. The two cumulative dose regimens produced almost identical bronchodilator responses at each time point. The relative dose-potency between the 800- and 400-mug cumulative dose regimens was 0.7 with a 95% confidence interval of 0.5-1.0, excluding the true value of 2. The 400-mug cumulative dose regimen resulted in a higher FEV, at 115 min than the 400-mug single-dose regimen. There was no difference in the bronchodilator response to the single dose of 50, 100, or 400 mug of salbutamol after either 5 or 25 min. Thus, care should be exercised when using either a cumulative or single-dose design for comparing different beta (2)-agonists, or different inhalation devices, with respect to their relative dose-potency. In addition, this study provides further evidence that for short-acting beta (2)-agonists such as salbutamol, lower doses than those normally recommended may be used, and that repeated self-administration of low doses over a period of 60 min may give a better bronchodilator response than a single administration of a high dose.