BAY u3405, a thromboxane A(2) antagonist, reduces bronchial hyperresponsiveness in asthmatics
BAY u3405, a thromboxane A(2) antagonist, reduces bronchial hyperresponsiveness in asthmatics
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DOI：
10.1378/chest.109.2.338
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发表时间：
1996-02-01
期刊：
影响因子：
9.6
通讯作者：
Hara, N
中科院分区：
文献类型：
--
作者：
Aizawa, H;Shigyo, M;Hara, N
目的：血栓素A（2）（TXA（2））可诱导支气管高反应性，沿着对平滑肌的支气管收缩作用。我们研究了TXA（2）拮抗剂BAY u3405对哮喘患者支气管对乙酰甲胆碱（MCh）高反应性的影响。患者：12名成人哮喘患者以随机、双盲、安慰剂对照、交叉的方式进行研究。设计：在2周的导入期后，在交叉设计中，受试者口服75 mg BAY u3405或安慰剂，每天两次，每次持续2周，插入2周的洗脱期。用Astograph法测定支气管高反应性。简而言之，在连续吸入MCh的过程中，通过强制振荡法测量呼吸阻力（Brs），逐步增加浓度，直到Rrs达到基线值的两倍。支气管高反应性评价为诱导Rrs增加的MCh最小累积剂量（Dmin）。Dmin的计算，使1 U的Dmin等于1分钟的吸入的气雾剂溶液在1.0 mg/mL在安静的breathing.Results：3名受试者退出评估，因为他们有哮喘发作或喘息在研究期间。BAY u3405治疗后0.533 U（GSEM 1.675）的Dmin值显著大于安慰剂治疗后0.135 U（GSEM 1.969）的Dmin值（p=0.0139）。有没有安全性问题，在任何治疗group.Conclusion：我们得出结论，BAY u3405可能是一个有用的药物衰减支气管哮喘的支气管高反应性。
Objectives: Thromboxane A(2) (TXA(2)) is reported to induce bronchial hyperresponsiveness along with the well-documented bronchoconstrictor action on smooth muscles. We examined the effect of the TXA(2) antagonist, BAY u3405, on bronchial hyperresponsiveness to methacholine (MCh) in asthmatics.Patients: Twelve adult asthmatics were studied in a randomized, double-blind, placebo-controlled, crossover fashion.Design: Following a 2-week run-in period, the subjects were administered 75 mg of BAY u3405 or placebo orally, twice a day for 2 weeks each in a crossover design, interposing a 2-week washout period. Bronchial hyperresponsiveness was measured by the astograph method. Briefly, the respiratory resistance (Brs) was measured by the forced oscillation method during continuous inhalation of MCh in stepwise incremental concentrations, until Rrs reached twice the baseline value. Bronchial hyperrresponsiveness was evaluated as the minimum cumulative dose (Dmin) of MCh that induced an increase in Rrs. Dmin was calculated so that 1 U of Dmin equals to 1 min of inhalation of aerosol solution at 1.0 mg/mL during quiet breathing.Results: Three subjects were withdrawn from the evaluation because they had asthmatic attacks or wheezing during the study. The Dmin value of 0.533 U (GSEM 1.675) after the BAY u3405 treatment was significantly greater than that of 0.135 U (GSEM 1.969) after the placebo treatment (p=0.0139). There were no safety concerns in either treatment group.Conclusion: We conclude that BAY u3405 may be a useful drug for attenuating bronchial hyperresponsiveness in bronchial asthma.