TY - JOUR T1 -噻托溴铵，一种新的长效抗马碱型支气管扩张剂:慢性阻塞性肺疾病(COPD)患者的药效学研究荷兰研究组JF -欧洲呼吸杂志JO - Eur Respir J SP - 1506 LP - 1513 DO - 10.1183/09031936.95.08091506 VL - 8 IS - 9 AU - Maesen, FP AU - Smeets, JJ AU - Sledsens, TJ AU - Wald, FD AU - Cornelissen，PJ Y1 - 1995/09/01 UR - //www.qdcxjkg.com/content/8/9/1506.abstract N2 -本研究的目的是研究新开发的抗马碱剂噻托溴铵在慢性阻塞性肺疾病(COPD)患者中的支气管扩张剂疗效和作用时间的剂量依赖性。在一项随机、双盲、安慰剂对照、交叉设计中，患者吸入单剂量10-80微克噻托溴铵和安慰剂，以乳糖粉胶囊形式配制。试验剂量之间的洗脱期为72小时。35名患者参加了试验(32名男性和3名女性;平均年龄64岁)。基线1秒用力呼气量(FEV1)(平均1.34 L)低于预测值的65%，为<用力肺活量(FVC)的70%所有受试者均有超过10包年的吸烟史。吸入40微克异丙托溴铵后FEV1的平均可逆性为28%。 Pulmonary function testing was performed before and at regular time intervals for up to 32 h after test drug administration. Compared to placebo, tiotropium bromide produced significant improvements in FEV1, FVC, peak expiratory flow rate (PEFR) and forced mid-expiratory flow (FEF25-75%). The bronchodilator response was almost immediate; 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. ER -