The aim of this double-blind, double-dummy, crossover, randomised, pilot study was to explore the acute effects of adding salmeterol and tiotropium in patients with stable COPD. A total of 20 outpatients with stable COPD were enrolled. Single doses of 18-μg tiotropium, 50-μg salmeterol, and 18-μg tiotropium+50-μg salmeterol were given. Serial measurements of forced expiratory volume in 1 s (FEV1) were performed over 24 h. The mean maximum increases in FEV1 from pre-dosing value on each of the dosing days were 0.165 l (95% CI: 0.098-0.232) for tiotropium, 0.241 l (95% CI: 0.151-0.332) for salmeterol, and 0.290 l (95% CI: 0.228-0.353) for the combination and occurred 4 h after inhalation of tiotropium or salmeterol and 3 h after the combination. At 12 h, the mean increases in FEV1 from pre-dosing value were 0.071 l (95% CI: 0.001-0.141; P=0.047) for tiotropium, 0.069 l (95% CI: 0.018-0.120; P=0.010) for salmeterol, and 0.108 l (95% CI: 0.047-0.170; P=0.001) for the tiotropium+salmeterol combination. Only the difference between salmeterol and tiotropium+salmeterol was statistically significant (P=0.009). At 24 h, the mean FEV1 value was still higher than the mean pre-dosing value for tiotropium (0.042 l; 95% CI: -0.012-0.097; P=0.119) and the tiotropium+salmeterol combination (0.051 l; 95% CI: 0.015-0.087; P=0.007), but not for salmeterol alone (-0.013 l; 95% CI: -0.041-0.014; P=0.324). The FEV1 area under the curve (AUCs0-12h) were 1.657 l (95% CI: 1.152-2.162) for tiotropium, 2.068 l (95% CI: 1.385-2.752) for salmeterol, and 2.541 l (95% CI: 1.954-3.129) for tiotropium+salmeterol. Only the difference between tiotropium and the tiotropium+salmeterol combination was statistically significant (P=0.01). The FEV1 AUCs0-24h were 2.854 l (95% CI: 1.928-3.780) for tiotropium, 2.786 l (95% CI: 1.913-3.660) for salmeterol, and 3.640 l (95% CI: 2.674-4.605) for tiotropium+salmeterol. All differences between treatments were not statistically significant (P>0.05). These results seem to indicate that the use of the tiotropium+salmeterol combination is more efficacious than the single agents alone, but the once-daily administration of the two drugs is inadvisable due to the broncholytic profile of salmeterol.
- Combination therapy
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine