文摘
本研究的目的是探讨支气管扩张剂存在剂量依赖的相关性的作用效果和持续时间的新开发antimuscarinic溴化剂tiotropium在慢性阻塞性肺疾病(COPD)患者。在一项随机,双盲,安慰剂对照,交叉设计,病人吸入单溴化剂10 - 80微克tiotropium和安慰剂,制定在乳糖粉胶囊。测试剂72 h之间的洗脱期。三十五参与试验的患者(32名男性和3女性;平均年龄64岁)。基线在一秒用力呼气量(FEV1)(平均1.34 L)不到65%的预测,< 70%的用力肺活量(FVC)。所有受试者超过10包年吸烟史的人。平均FEV1吸入后的可逆性40微克ipratropium溴化是28%。肺功能测试之前执行,以固定时间间隔长达32 h后测试药物管理局。与安慰剂相比,tiotropium溴化产生显著改善残,FVC,呼气流速峰值(病人),迫使mid-expiratory流(fef25 - 75%)。支气管扩张剂反应几乎是立即; peak improvement in FEV1 was reached 1-4 h after test drug inhalation, and the duration of action extended to 32 h after the 20, 40 and 80 micrograms doses. A clear dose-response relationship was seen for peak FEV1 and for the average FEV1 over differing time periods during the 32 h observation period, 80 micrograms of test drug being superior to the 10 micrograms dose. Peak improvement in FEV1 ranged 19-26% of test-day baseline for tiotropium bromide doses compared to 16% for placebo. The large improvement for placebo is probably due to carry-over effect which was significant. After excluding carry-over effect, the peak response to placebo decreased to 11%, whilst for tiotropium bromide doses it ranged 20-25%; standard error for mean difference was about 4%. There was no evidence of systemic anticholinergic effects. In this population of patients with COPD, tiotropium bromide was found to be a safe and long-acting bronchodilator, demonstrating a clear dose-response relationship following single dose administration.