Dose-response relationship: fenoterol, ipratropium bromide and their combination

The beta agonist fenoterol, the antimuscarinic ipratropium bromide and their combination were compared in 10 patients with stable reversible airway obstruction. A single-blind cross-over design was used in order to obtain cumulative dose-response curves. The dose inhaled by an IPPB apparatus on different days were: fenoterol, from 12.5 to 1.600 cumulate micrograms; ipratropium bromide, from 5 to 640 cumulate micrograms; combination (5:2), from 17.5 to 1.120 cumulate micrograms. The bronchodilator effect was measured as changes of FEV1 and of SGaw. Data were processed in order to identify the median effective dose (ED50) and the percentage change at ED50 (RED50). The mean ED50 in micrograms (+/- SD) resulted in: Fenoterol, ED50 (FEV1) = 132 (+/- 46); ED50 (SGaw) = 172 (+/- 62); Ipratropium bromide, ED50 (FEV1) = 14 (+/- 7); ED50 (SGaw) = 23 (+/- 11); Combination, ED50 (FEV1) = 109 (+/- 26); ED50 (SGaw) = 121 (+/- 53). The mean RED50% (+/- SD) resulted in: Fenoterol, RED50 (FEV1) = 30 (+/- 16); RED50 (SGaw) = 106 (+/- 78); Ipratropium bromide, RED50 (FEV1) = 21 (+/- 10); RED50 (SGaw) = 82 (+/- 66); Combination, RED50 (FEV1) = 35 (+/- 11) RED50 (SGaw) = 135 (+/- 81). The ED50 (FEV1) of the combination was significantly lower (p less than 0.05) than that of fenoterol. This increased potency of the combination supports evidence for an overadditive interaction between fenoterol and ipratropium bromide. Moreover, the efficacy of fenoterol (RED50) is enhanced by combining the two drugs.