Dose-response characteristics of nebulized fenoterol in asthmatic children

Fenoterol hydrobromide, a beta 2-selective bronchodilator, was administered by aqueous nebulization to 31 children with stable asthma. An initial comparison of 0, 100, 300, and 1000 micrograms drug in 20 of these patients showed a significant change in forced expiratory volume in 1 second for all three doses compared with change after placebo (P less than 0.0001). However, the differences in peak pulmonary response from 100 to 1000 micrograms were not large (P greater than 0.2). Assessment of spirometric responses of 11 children to 3, 10, 30, or 100 micrograms nebulized fenoterol clearly revealed the dose-response effect (P less than 0.01). When all the FEV1 data were plotted over the entire range of 3 to 1000 micrograms, the resultant log dose vs response curve could be characterized by the ED50, the amount of drug producing half-maximal response. At 15, 30, or 60 minutes, the ED50 was in the range 8 to 10 micrograms. With increasing time there was a parallel shift of the entire dose response curve to the right, manifested by ED50 of 47 and 150 micrograms at two and three hours, respectively, after administration. This decreasing potency of a sympathomimetic drug with time shows that duration of effect and dosage are interdependent variables and must be evaluated simultaneously. Such considerations cannot be derived from cumulative dose-response studies. In our patients, 100 to 300 micrograms fenoterol delivered by aqueous nebulization achieved optimal bronchodilation with no detectable cardiovascular side effects.