Krefting Research Centre, Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Pulm Pharmacol Ther. 2011 Feb;24(1):55-8. doi: 10.1016/j.pupt.2010.10.006. Epub 2010 Oct 28.
According to the duration of bronchodilation, beta-2-agonists are divided into short and long acting bronchodilators. The bronchodilatory effect of available long acting beta-2-agonists (LABAs) beyond 12 h is not sufficiently studied. In order to evaluate the bronchodilatory effects of LABA in subjects without airway obstruction, the measurement of specific airway conductance (sGaw) with whole body plethysmography has been demonstrated to be a sensitive method. We aimed to determine the bronchodilatory effects of single doses of salmeterol 25, 50 and 200 μg and salbutamol 200 μg in healthy subjects (n = 16) over a 24 h period in a randomized, double-blind, triple-dummy, placebo-controlled cross-over-study. At the 12-h endpoint, all three doses of salmeterol significantly increased sGaw compared with placebo. At the 24-h endpoint, there was a significant increase in sGaw with salmeterol 200 μg, while with 25 and 50 μg salmeterol the sGaw increase failed to reach statistical significance. There was no statistically significant increase in sGaw with salbutamol 200 μg at either the 12-h or 24-h endpoints. For weighted means, all three salmeterol doses showed statistically significant increase in sGaw compared with placebo over 0-12, 12-24 and 0-24 h periods, while for salbutamol 200 μg a significant increase in sGaw was recorded only over 0-12 h period. We conclude that sGaw measurement is a suitable method for recording the bronchodilatory effect of beta-2-agonists in healthy subjects. Using this method we could demonstrate that salmeterol 200 μg provides significant increase in specific airway conductance up to 24 h after a single dose.
根据支气管扩张持续时间，β-2-激动剂分为短效和长效支气管扩张剂。现有长效β-2-激动剂（LABA）超过 12 小时的支气管扩张作用尚未得到充分研究。为了评估 LABA 在无气道阻塞受试者中的支气管扩张作用，全身 plethysmography 测量特定气道传导率（sGaw）已被证明是一种敏感的方法。我们旨在确定沙美特罗 25、50 和 200μg 以及沙丁胺醇 200μg 单剂量在健康受试者（n=16）中的支气管扩张作用，在一项随机、双盲、三盲、安慰剂对照交叉研究中进行 24 小时。在 12 小时终点时，所有三种剂量的沙美特罗与安慰剂相比均显著增加 sGaw。在 24 小时终点时，沙美特罗 200μg 剂量显著增加 sGaw，而沙美特罗 25 和 50μg 剂量增加未达到统计学意义。沙丁胺醇 200μg 在 12 小时或 24 小时终点时均未引起 sGaw 统计学显著增加。对于加权平均值，与安慰剂相比，所有三种沙美特罗剂量在 0-12、12-24 和 0-24 小时期间 sGaw 均有统计学显著增加，而沙丁胺醇 200μg 仅在 0-12 小时期间 sGaw 增加具有统计学意义。我们得出结论，sGaw 测量是记录健康受试者中β-2-激动剂支气管扩张作用的合适方法。使用这种方法，我们可以证明沙美特罗 200μg 在单次给药后 24 小时内可显著增加特定气道传导率。
