Formoterol and salmeterol in partially reversible chronic obstructive pulmonary disease: A crossover, placebo-controlled comparison of onset and duration of action

Background: In contrast to the well-known activity profile in asthma, the p recise efficacy and optimum dose schedules of long-acting beta(2)-agonists in chronic obstructive pulmonary disease (COPD) are not clear. Objective: I n this study, we aimed to compare the onset and the duration of action of a single inhalation of formoterol and salmeterol in COPD patients having par tially reversible airway obstruction. Methods: In a double-blind, randomize d, crossover and placebo-controlled study design, the respiratory functions of 22 patients (mean age 57.3 +/- 5.4 years) having mild to severe COPD (5 mild, 8 moderate and 9 severe) and partially reversible airway obstruction [mean baseline reversibility of forced expiratory volume in 1 s (FEV1) 19. 3 +/- 3.1%] were evaluated after inhalation of 12 mu g formoterol and 50 mu g salmeterol. Results: Regarding the onset of bronchodilator action, the m ean absolute increase of 0.20 liters in FEV1 10 min after inhalation of for moterol was significantly higher than baseline and that of placebo (0.04 li ters), whereas that of salmeterol (0.11 liters) did not reach statistical s ignificance. At 20 min, both formoterol (0.25 liters) and salmeterol (0.20 liters) produced a significant increase in FEV1 compared with baseline and with that of placebo (0.04 liters). The peak bronchodilator effects occurri ng at 60 and 120 min following formoterol (0.39 liters) and salmeterol (0.4 0 liters) inhalation, respectively, were significantly higher than the corr esponding levels of placebo (0.02 and -0.12 liters, respectively). Concerni ng the duration of action, the 12-hour values of both formoterol (0.25 lite rs) and salmeterol (0.22 liters) were significantly higher than that of pla cebo (-0.12 liters). The area under the curve values of FEV1 of formoterol (3.5 +/- 1.3 l.h) and salmeterol (3.2 +/- 1.2 l.h) averaged over 12 h were comparable and higher than placebo values (1.2 +/- 0.5 l.h). After formoter ol inhalation 2 patients experienced tremor and 1 had palpitation; 1 tremor and 1 headache attack were noted after salmeterol. For the pharmacological ly predictable side effects, there was no difference between the drugs. Con clusions: In conclusion, this study revealed that a single dose of 12 mu g formoterol and 50 mu g salmeterol provided comparable bronchodilation withi n 12 h and had tolerable side effects in patients with mild to severe COPD having partially reversible airway obstruction.