The functional impact of adding salmeterol and tiotropium in patients with stable COPD.
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-microg tiotropium, 50-microg salmeterol, and 18-microg tiotropium+ 50-microg salmeterol were given. Serial measurements of forced expiratory volume in 1 s (FEV1) were performed over 24h. The mean maximum increases in FEV1 from pre-dosing value on each of the dosing days were 0.165l (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 12h, 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 24h, 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: 0.01 5-0.087; 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 (95l 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.
Cazzola
M
M
Department of Respiratory Medicine, Antonio Cardarelli Hospital, Via del Parco Margherita 24, Napoli 80121, Italy. mcazzola@qubisoft.it
Centanni
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S
Santus
P
P
Verga
M
M
Mondoni
M
M
di Marco
F
F
Matera
M G
MG
D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000886:Anthropometry; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D000069447:Tiotropium Bromide; D014797:Vital Capacity / Q000187:drug effects
D001993:Bronchodilator Agents; D004338:Drug Combinations; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D010100:Oxygen; D000069447:Tiotropium Bromide