Dose-response curves to inhaled beta-adrenoceptor agonists in normal and asthmatic subjects

Abstract

We have compared bronchodilator dose-response curves to inhaled salbutamol in seven normal and eight asthmatic subjects. In all normal subjects maximal bronchodilatation measured by partial flow volume curves was achieved at a cumulative dose of 110 micrograms. The dose necessary to produce half maximal response (ED50) was 23 +/- 2 micrograms (mean +/- s.e. mean) with a range of 18-28 micrograms. In asthmatic subjects maximal bronchodilatation measured by FEV1 and by maximal flow volume curves was achieved at significantly higher (P less than 0.01) doses of salbutamol with a mean ED50 of 83 +/- 28 micrograms and range of 25-251 micrograms. There was a significant (P less than 0.05) correlation between ED50 and % predicted baseline FEV1. This is more likely to reflect impaired access of drug for airway beta-adrenoceptors than impaired beta-adrenoceptor function in asthma. In five asthmatic subjects dose-response curves to salbutamol and isoprenaline were compared and found to be similar, thus providing no evidence that salbutamol is a partial agonist in vivo, as it appears to be in vitro.