Cazzola M, Centanni S, Santus P, Verga M, Mondoni M, di Marco F, Matera M G
Department of Respiratory Medicine, Antonio Cardarelli Hospital, Via del Parco Margherita 24, Napoli 80121, Italy.
Respir Med. 2004 Dec;98(12):1214-21. doi: 10.1016/j.rmed.2004.05.003.
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.
这项双盲、双模拟、交叉、随机的试点研究旨在探讨在稳定期慢性阻塞性肺疾病（COPD）患者中加用沙美特罗和噻托溴铵的急性效应。共纳入20例稳定期COPD门诊患者。分别给予单剂量18μg噻托溴铵、50μg沙美特罗以及18μg噻托溴铵 + 50μg沙美特罗。在24小时内对1秒用力呼气容积（FEV1）进行连续测量。各给药日FEV1相对于给药前值的平均最大增加量分别为：噻托溴铵0.165升（95%CI：0.098 - 0.232），沙美特罗0.241升（95%CI：0.151 - 0.332），联合用药0.290升（95%CI：0.228 - 0.353），且在吸入噻托溴铵或沙美特罗后4小时以及联合用药后3小时出现。在12小时时，噻托溴铵的FEV1相对于给药前值的平均增加量为0.071升（95%CI：0.001 - 0.141；P = 0.047），沙美特罗为0.069升（95%CI：0.018 - 0.120；P = 0.010），噻托溴铵 + 沙美特罗联合用药为0.108升（95%CI：0.047 - 0.170；P = 0.001）。仅沙美特罗与噻托溴铵 + 沙美特罗之间的差异具有统计学意义（P = 0.009）。在24小时时，噻托溴铵的平均FEV1值仍高于给药前值（0.042升；95%CI： - 0.012 - 0.097；P = 0.119），噻托溴铵 + 沙美特罗联合用药也高于给药前值（0.051升；95%CI：0.015 - 0.087；P = 0.007），但单独使用沙美特罗时未高于给药前值（ - 0.013升；95%CI： - 0.041 - 0.014；P = 0.324）。FEV1曲线下面积（AUCs0 - 12h）分别为：噻托溴铵1.657升（95%CI：1.152 - 2.162），沙美特罗2.068升（95%CI：1.385 - 2.752），噻托溴铵 + 沙美特罗2.541升（95%CI：1.954 - 3.129）。仅噻托溴铵与噻托溴铵 + 沙美特罗联合用药之间的差异具有统计学意义（P = 0.01）。FEV1 AUCs0 - 24h分别为：噻托溴铵2.854升（95%CI：1.928 - 3.780），沙美特罗2.786升（95%CI：1.913 - 3.660），噻托溴铵 + 沙美特罗3.640升（95%CI：2.674 - 4.605）。各治疗组之间所有差异均无统计学意义（P>0.05）。这些结果似乎表明，噻托溴铵 + 沙美特罗联合用药比单一药物更有效，但由于沙美特罗的支气管舒张特性，这两种药物每日一次给药并不可取。
