吸入性VPAC(2)受体激动剂对稳定期哮喘患者的支气管扩张作用。
Bronchodilation by an inhaled VPAC(2) receptor agonist in patients with stable asthma.
作者信息
Lindén A, Hansson L, Andersson A, Palmqvist M, Arvidsson P, Löfdahl C-G, Larsson P, Lötvall J
机构信息
Department of Respiratory Medicine and Allergology, Göteborg University, Guldhedsgatan 10A, S-413 46 Göteborg, Sweden.
出版信息
Thorax. 2003 Mar;58(3):217-21. doi: 10.1136/thorax.58.3.217.
BACKGROUND
The synthetic vasoactive intestinal peptide (VIP) analogue Ro 25-1553 is a selective VIP-PACAP type 2 (VPAC(2)) receptor agonist that causes a bronchodilatory effect in guinea pigs in vivo. The effect of Ro 25-1553 given by inhalation to patients with asthma was studied and compared with that of a long acting beta(2) adrenoceptor agonist.
METHODS
Twenty four patients with moderate stable asthma participated in a double blind, randomised, placebo controlled, crossover study. The primary variable was bronchodilatory effect (increase in forced expiratory volume in 1 second, FEV(1)) after inhalation of Ro 25-1553 (100 microg or 600 microg) and formoterol (4.5 microg), respectively. Putative side effects were characterised by monitoring sitting blood pressure, serum potassium, electrocardiography and echocardiography.
RESULTS
Inhalation of 600 microg Ro 25-1553 caused a rapid bronchodilatory effect (geometric mean increase in FEV(1) compared with placebo) within 3 minutes of 6% (95% CI 4 to 9), as did inhalation of formoterol (8% (95% CI 5 to 10)). The corresponding maximum bronchodilatory effect during 24 hours was similar for 600 microg Ro 25-1553 (7% (95% CI 4 to 10)) and the reference bronchodilator formoterol (10% (95% CI 7 to 12)). However, for both doses of Ro 25-1553 the bronchodilatory effect was attenuated 5 hours after inhalation whereas formoterol still had a bronchodilatory effect 12 hours after inhalation. Neither Ro 25-1553 nor formoterol produced any clinically relevant side effects. No drug related difference in adverse events was observed.
CONCLUSION
Inhalation of a synthetic selective VPAC(2) receptor agonist constitutes a promising approach for bronchodilation in patients with asthma.
背景
合成血管活性肠肽（VIP）类似物Ro 25 - 1553是一种选择性VIP - 垂体腺苷酸环化酶激活肽2型（VPAC(2)）受体激动剂，在豚鼠体内可产生支气管舒张作用。本研究将Ro 25 - 1553吸入给药于哮喘患者的效果与长效β(2)肾上腺素能受体激动剂的效果进行了比较。
方法
24例中度稳定哮喘患者参与了一项双盲、随机、安慰剂对照、交叉研究。主要变量为分别吸入Ro 25 - 1553（100微克或600微克）和福莫特罗（4.5微克）后的支气管舒张作用（一秒用力呼气容积增加量，FEV(1)）。通过监测坐位血压、血清钾、心电图和超声心动图来表征可能的副作用。
结果
吸入600微克Ro 25 - 1553在3分钟内产生快速支气管舒张作用（与安慰剂相比，FEV(1)的几何平均增加量）为6%（95%可信区间4至9），吸入福莫特罗时为8%（95%可信区间5至10）。24小时内相应的最大支气管舒张作用，600微克Ro 25 - 1553为7%（95%可信区间4至10），对照支气管扩张剂福莫特罗为10%（95%可信区间7至12）。然而，两种剂量的Ro 25 - 1553吸入后5小时支气管舒张作用减弱，而福莫特罗吸入后12小时仍有支气管舒张作用。Ro 25 - 1553和福莫特罗均未产生任何临床相关副作用。未观察到药物相关的不良事件差异。
结论
吸入合成选择性VPAC(2)受体激动剂是哮喘患者支气管扩张的一种有前景的方法。
Zotero 插件