Bronchodilating activity of two new beta2 agonists: Study of dose-response curves by probit analysis

Abstract

Eleven asthmatic subjects with reversible airway obstruction were examined in order to evaluate the potency, effectiveness, and side effects of two new beta2 agonist agents, naminterol and etanterol, compared with those of inhaled placebo. Dose-response curves were constructed plotting the cumulative log doses (from 50 to 3,200 \u3bcg delivered from an intermittent positive pressure breathing device) with the induced changes of forced expiratory volume in one second (FEV1) and specific conductance of airways (SGaw) after the inhalation of each dose of the agents under investigation. By probit regression analysis we obtained the median effective dose (ED50) with its fiducial limits (mean \ub1 SE) for FEV1 (naminterol: 131 \ub1 25 \u3bcg; etanterol: 174 \ub1 33 \u3bcg) and SGaw (naminterol: 159 \ub1 25 \u3bcg; etanterol: 199 \ub1 38 \u3bcg) and the effects at ED50 on FEV1 (naminterol: 22.4 \ub1 4.0%, etanterol: 27.6 \ub1 5.0%) and SGaw (naminterol: 94.5 \ub1 14.9%; etanterol: 119.4 \ub1 14.9%). We regarded these values as indexes of the potency and the effectiveness of the agents, respectively. The cardiovascular parameters (systolic and diastolic arterial pressure and heart rate) did not change significantly after any dose with the exception of a significant fall (4.9 mmHg) of systolic pressure after the inhalation of 800 \u3bcg of etanterol. No patient complained of tremor. Both drugs showed good bronchodilating activity without significant cardiovascular or muscular side effects. At ED50, etanterol induced a larger effect of FEV1 and SGaw than naminterol