Reiss T F, Altman L C, Chervinsky P, Bewtra A, Stricker W E, Noonan G P, Kundu S, Zhang J
Department of Pulmonary/Immunology, Merck Research Laboratories, Rahway, NJ 07065, USA.
J Allergy Clin Immunol. 1996 Sep;98(3):528-34. doi: 10.1016/s0091-6749(96)70086-6.
Cysteinyl leukotrienes mediate signs and symptoms of asthma. In a double-blind, placebo-controlled, crossover study, a new potent and specific cysteinyl leukotriene (LTD4) receptor antagonist, montelukast (MK-0476), was evaluated for tolerability and clinical efficacy in patients with chronic asthma (receiving and not receiving inhaled corticosteroids).
Twenty-nine nonsmoking patients with asthma (15 treated concomitantly with inhaled corticosteroids) with FEV1 percent predicted values between 50% to 80% received MK-0476, 200 mg, or placebo three times daily for 10 1/3 days (31 doses) in a random, crossover manner, after a 2-week, open, baseline period. Comparisons in FEV1 (mean percent change from baseline after the first and last dose), mean daily daytime asthma and nocturnal awakening scores, and mean daily beta-agonist use were made between treatment periods.
Montelukast, compared with placebo, caused improvements in FEV1 (mean percentage point difference of the percentage change from baseline) 3 and 4 hours after dosing on day 1 (hour 3, 9.0%; 95% confidence interval [CI] 0.53, 18.72; hour four, 10.9%; 95% CI -0.25, 20.20) and day 11 (hour 3, 14.0%; 95% CI 0.76, 31.43; hour 4, 13.4%; 95% CI 1.24, 28.83). Reductions were observed in mean daily beta-agonist use (1.0 puff/day [95% CI -1.61, -0.26]), mean daytime symptom scores, and nocturnal awakenings over the 10 1/3 day treatment period. There were no important differences between the groups receiving and those not receiving inhaled corticosteroids. Montelukast was well tolerated with no serious clinical adverse events reported.
In this study Montelukast, 200 mg, administered three times daily for 10 1/3 days, compared with placebo, was generally well tolerated and resulted in significant improvement in chronic asthma, irrespective of the presence of inhaled corticosteroids.
半胱氨酰白三烯介导哮喘的体征和症状。在一项双盲、安慰剂对照、交叉研究中，对一种新型强效特异性半胱氨酰白三烯（LTD4）受体拮抗剂孟鲁司特（MK - 0476）在慢性哮喘患者（接受和未接受吸入性糖皮质激素治疗）中的耐受性和临床疗效进行了评估。
29名非吸烟哮喘患者（15名同时接受吸入性糖皮质激素治疗），其FEV1预测值百分比在50%至80%之间，在为期2周的开放基线期后，以随机、交叉方式每日3次接受200 mg孟鲁司特或安慰剂治疗，持续10又1/3天（31剂）。对治疗期之间的FEV1（首剂和末剂后相对于基线的平均变化百分比）、每日白天哮喘和夜间觉醒评分均值以及每日β受体激动剂使用均值进行比较。
与安慰剂相比，孟鲁司特在第1天给药后3小时和4小时（第3小时，9.0%；95%置信区间[CI] 0.53，18.72；第4小时，10.9%；95% CI -0.25，20.20）以及第11天给药后3小时和4小时（第3小时，14.0%；95% CI 0.76，31.43；第4小时，13.4%；95% CI 1.24，28.83）使FEV1得到改善。在为期10又1/3天的治疗期内，每日β受体激动剂使用均值（1.0喷/天[95% CI -1.61，-0.26]）、白天症状评分均值和夜间觉醒次数均有所减少。接受和未接受吸入性糖皮质激素治疗的组之间无重要差异。孟鲁司特耐受性良好，未报告严重临床不良事件。
在本研究中，每日3次给予200 mg孟鲁司特治疗10又1/3天，与安慰剂相比，总体耐受性良好，且无论是否使用吸入性糖皮质激素，均可使慢性哮喘得到显著改善。
