Cumulative and single-dose design to assess the bronchodilator effects of beta(2)-agonists in individuals with asthma

dWith the development of different chlorofluorocarbon (CFC)-free metered do se aerosol and dry powder devices, it is necessary to study and validate th e methods used for assessing and comparing their efficacy. This study evalu ated the cumulative dose design by determining the bronchodilator response to salbutamol given according to either a high or a low cumulative dose reg imen. Adults with asthma (n = 24) were studied in a placebo-controlled, ran domized, double-blind, cross-over design. On separate days, cumulative dose s of salbutamol (50+50+100+200 or 100+100+200+400 or 400+0+0+0 or 0+0+0+0 m ug) were given via Turbuhaler with 30 min between doses. The two cumulative dose regimens produced almost identical bronchodilator responses at each t ime point. The relative dose-potency between the 800- and 400-mug cumulativ e dose regimens was 0.7 with a 95% confidence interval of 0.5-1.0, excludin g the true value of 2. The 400-mug cumulative dose regimen resulted in a hi gher FEV, at 115 min than the 400-mug single-dose regimen. There was no dif ference in the bronchodilator response to the single dose of 50, 100, or 40 0 mug of salbutamol after either 5 or 25 min. Thus, care should be exercise d when using either a cumulative or single-dose design for comparing differ ent beta (2)-agonists, or different inhalation devices, with respect to the ir relative dose-potency. In addition, this study provides further evidence that for short-acting beta (2)-agonists such as salbutamol, lower doses th an those normally recommended may be used, and that repeated self-administr ation of low doses over a period of 60 min may give a better bronchodilator response than a single administration of a high dose.