Noonan M J, Chervinsky P, Brandon M, Zhang J, Kundu S, McBurney J, Reiss T F
Allergy Associates, PC Research, Portland, Oregon, USA.
Eur Respir J. 1998 Jun;11(6):1232-9. doi: 10.1183/09031936.98.11061232.
The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antagonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase (absolute value) after beta2-agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05; linear trend test) different from placebo. All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate (PEFR) that were significantly (p<0.05) different from placebo. Differences (least square mean) between the pooled 10 and 50 mg montelukast treatment groups and placebo were: 7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use (puff x day(-1)). The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments. We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points.
白三烯是已知的支气管哮喘重要介质。在一项安慰剂对照、多中心、平行组研究中，对强效选择性半胱氨酰白三烯1（CysLT1）受体拮抗剂孟鲁司特改善慢性哮喘的剂量相关性能力进行了研究。在为期两周的安慰剂导入期后，将一秒用力呼气容积（FEV1）为预测值40%-80%且使用β2激动剂后增加≥15%（绝对值）的慢性哮喘患者随机分配至四个治疗组之一（安慰剂或孟鲁司特2、10或50 mg，每晚一次），进行为期三周的双盲治疗期。对于患者报告的终点（日间症状评分、按需使用吸入β2激动剂、哮喘特异性生活质量）和哮喘加重频率，孟鲁司特10 mg和50 mg引起的反应相似，优于2 mg，且与安慰剂有显著差异（p<0.05；线性趋势检验）。所有三个剂量均使FEV1以及早晚呼气峰值流速（PEFR）得到改善，与安慰剂有显著差异（p<0.05）。孟鲁司特10 mg和50 mg合并治疗组与安慰剂之间的差异（最小二乘均值）为：FEV1相对于基线变化7.1%，早晨PEFR为19.23 L·min-1，日间哮喘症状评分（绝对值）为-0.29，β2激动剂使用量为-0.82（吸·天-1）。不良事件发生率与剂量无关，孟鲁司特治疗组与安慰剂治疗组之间也无差异。我们得出结论，孟鲁司特在2-50 mg范围内可使患者报告的哮喘终点得到剂量相关性改善。孟鲁司特通过改善哮喘控制终点使慢性哮喘患者获益。
