Background: In contrast to the well-known activity profile in asthma, the precise efficacy and optimum dose schedules of long-acting β2-agonists in chronic obstructive pulmonary disease (COPD) are not clear. Objective: In 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 partially reversible airway obstruction. Methods: In a double-blind, randomized, 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 μg formoterol and 50 μg salmeterol. Results: Regarding the onset of bronchodilator action, the mean absolute increase of 0.20 liters in FEV1 10 min after inhalation of formoterol was significantly higher than baseline and that of placebo (0.04 liters), whereas that of salmeterol (0.11 liters) did not reach statistical significance. 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 occurring at 60 and 120 min following formoterol (0.39 liters) and salmeterol (0.40 liters) inhalation, respectively, were significantly higher than the corresponding levels of placebo (0.02 and –0.12 liters, respectively). Concerning the duration of action, the 12-hour values of both formoterol (0.25 liters) and salmeterol (0.22 liters) were significantly higher than that of placebo (–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 formoterol inhalation 2 patients experienced tremor and 1 had palpitation; 1 tremor and 1 headache attack were noted after salmeterol. For the pharmacologically predictable side effects, there was no difference between the drugs. Conclusions: In conclusion, this study revealed that a single dose of 12 μg formoterol and 50 μg salmeterol provided comparable bronchodilation within 12 h and had tolerable side effects in patients with mild to severe COPD having partially reversible airway obstruction.

Keywords:
Chronic obstructive pulmonary disease, Formoterol, Salmeterol
1.
European Respiratory Society (ERS) Consensus statements: Optimal assessments and management of chronic obstructive pulmonary disease. Eur Respir J 1995;8:1398–1420.
2.
American Thoracic Society: Definitions, epidemiology, pathophysiology, diagnosis and staging of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152:S78–S83.
3.
Naline E, Zhang Y, Qian Y, Mairon N, Anderson GP, Grandordy B, Advenier C: Relaxant effects and durations of action of formoterol and salmeterol in the isolated human bronchus. Eur Respir J 1994;7:914–920.
4.
Tattersfield AE: Long-acting β2-agonists. Clin Exp Allergy 1992;22:600–605.
5.
Fitzpatrick MF, Mackay T, Driver H, Douglas NJ: Salmeterol in nocturnal asthma: A double blind, placebo controlled trial of a long acting inhaled β2 agonist. BMJ 1990;301:1365–1368.
6.
Ullman A, Hedner J, Svedmyr N: Inhaled salmeterol and salbutamol in asthmatic patients: An evaluation of asthma symptoms and the possible development of tachyphylaxis. Am Rev Respir Dis 1990;142:571–575.
7.
Tweeddale PM, Alexandre F, McHardy GJR: Short-term variability in FEV1 and bronchodilator responsiveness in patients with obstructive ventilatory defects. Thorax 1987;42:487–490.
8.
Weir DC, Sherwood BP: Measures of reversibility in response to bronchodilators in chronic airway obstruction: Relation to airway calibre. Thorax 1993;46:43–45.
9.
Korry RC, Callahan R, Baren HG, Syner JC: The veterans administration army cooperative study of pulmonary functions 1. Clinical spirometry in normal man. Am J Med 1961;30:243–258.
10.
Hedenström H, Wegener T, Boman G, Wahlander B: Effect of inhaled formoterol versus terbutaline on respiratory function in moderate bronchial asthma. Allergy 1992;47:158–163.
11.
Faurschou P: Chronic dose-ranging studies with salmeterol. Eur Respir Rev 1991;1:282–287.
12.
Schreurs AJM, Sinninghe Damsté HEJ, de Graaff CS, Greefhorst APM: A dose-response study with formoterol turbohaler as maintenance therapy in asthmatic patients. Eur Respir J 1996;9:1678–1683.
13.
Van Noord JA, Smeets JJ, Raaijmakers JAM, Bommer AM, Maesen FPV: Salmeterol versus formoterol in patients with moderately severe asthma: Onset and duration of action. Eur Respir J 1996;9:1684–1688.
14.
Newnham DM, Ingram CG, Earnshaw J, Palmer JBD, Dhillon DP: Salmeterol provides prolonged protection against exercise-induced bronchoconstriction in a majority of subjects with mild, stable asthma. Respir Med 1993;87:439–444.
15.
Cazzola M, Matera MG, Santangelo G, Vinciguerra A, Rossi F, D’Amato G: Salmeterol and formoterol in partially reversible severe chronic obstructive pulmonary disease: A dose-response study. Respir Med 1995;89:357–362.
16.
Cazzola M, Santangelo G, Piccolo A, Salzillo A, Matera MG, D’Amato G, Rossi F: Effect of salmeterol and formoterol in patients with chronic obstructive pulmonary disease. Pulm Pharmacol 1994;7:103–107.
17.
Rabe KF, Jörres R, Nowak D, Behr N, Magnussen H: Comparison of the effects of salmeterol and formoterol on airway tone and responsiveness over 24 hours in bronchial asthma. Am Rev Respir Dis 1993;147:1436–1441.
18.
Vollmer M, Schmidt EW, Ulmer WT: Responder and non-responder in the bronchodilator test? Pneumologie 1995;49:584–589.
19.
Vollmer M, Schmidt EW, Ulmer WT: Effect duration and treatment effectiveness of salmeterol, fenoterol and salbutamol in severe forms of respiratory tract obstruction. Pneumologie 1995;49:528–534.
20.
Ulrik CS: Efficacy of inhaled salmeterol in the management of smokers with chronic obstructive pulmonary disease: A single centre randomised, double blind, placebo-controlled, cross-over study. Thorax 1995;50:750–754.
1999
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