SALMETEROL AND FORMOTEROL IN PARTIALLY REVERSIBLE SEVERE CHRONIC OBSTRUCTIVE PULMONARY-DISEASE - A DOSE-RESPONSE STUDY

When testing the response to beta(2)-agonist drugs in severe chronic obstructive pulmonary disease (COPD), a dose-response assessment should be undertaken. This study compares the time course of inhaled salmeterol (25, 50 and 75 mu g) and formoterol (12, 24 and 36 mu g) at different doses in a group of 12 patients with partially reversible, but severe COPD (FEV(1) of 12-32% of predicted values after beta(2)-agonist drugs had been withheld for 24 h). All doses of salmeterol and formoterol induced a significant (P<0.01) spirometric improvement over the 12-h monitoring period, when compared to the spirometric improvement after placebo, but while formoterol induced a dose-dependent increase of the FVC, FEV(1) and FEV(50), this was not the case for salmeterol. In fact, 75 mu g salmeterol did not produce a further improvement of these parameters. Mean peak bronchodilation, expressed as the increase in FEV(1) over baseline values, occurred 2 h after inhalation of the three doses of salmeterol, and 1 h after inhalation of the three doses of formoterol. A comparison of 50 mu g salmeterol with 12 mu g or 24 mu g formoterol (clinically recommended doses), showed that improvement of FEV(1) after salmeterol was statistically (P<0.05) higher than that after the two doses of formoterol, although the mean peak bronchodilations were similar. This was because salmeterol has a longer duration of action than formoterol. These data demonstrate that salmeterol is equally effective as, but longer-acting than, formoterol at clinically recommended doses in patients suffering from COPD, with severe airway obstruction. Moreover, these data suggest that 50 mu g is the best dosage for salmeterol in these patients.