抽象的
本研究的目的是研究新开发的抗血清毒剂噻托溴铵患者慢性阻塞性肺病(COPD)患者的剂量依赖性支气管胆管疗效和作用持续时间。在随机,双盲,安慰剂控制,交叉设计中,患者吸入单剂量10-80微克噻托溴铵和安慰剂,配制在乳糖粉胶囊中。试验剂量之间的冲洗时间为72小时。在试验中注册了三十五名患者(32名男性和3名女性;平均64 YRS)。一秒钟(FEV1)(平均1.34L)的基线强制呼气量小于预测的65%,患有<70%的强制生命能力(FVC)。所有受试者都有10多个包装的吸烟历史。吸入40微克溴化溴铵后,FEV1的平均可逆性为28%。在试验药物管理后,在常规时间间隔之前和定期进行肺功能测试。与安慰剂相比,噻托溴铵在FEV1,FVC,峰值呼气流量(PEFR)中产生了显着的改善,并强制呼气流(FEF25-75%)。支气管扩张剂响应几乎是立即的; 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.