Reiss T F, Hill J B, Harman E, Zhang J, Tanaka W K, Bronsky E, Guerreiro D, Hendeles L
Department of Pulmonary/Immunology and Biostatistics, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Thorax. 1997 Dec;52(12):1030-5. doi: 10.1136/thx.52.12.1030.
A study was undertaken to determine whether montelukast, a new potent cysteinyl leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. The relationship between the urinary excretion of LTE4 and exercise-induced bronchoconstriction was also investigated.
Nineteen non-smoking asthmatic patients with a forced expiratory volume in one second (FEV1) of > or = 65% of the predicted value and a reproducible fall in FEV1 after exercise of at least 20% were enrolled. Subjects received placebo and montelukast 100 mg once daily in the evening or 50 mg twice daily, each for two days, in a three-period, randomised, double blind, crossover design. In the evening, approximately 20-24 hours after the once daily dose or 12 hours after the twice daily dose, a standardised exercise challenge was performed. Data from 14 patients were available for complete analysis.
The mean (SD) maximal percentage decrease in FEV1 after exercise was 29.6 (16.0), 17.1 (8.2), and 14.0 (9.4) for placebo, once daily, and twice daily regimens, respectively. The mean (95% CI) percentage protection was 37 (15 to 59) for the group who received 50 mg twice daily and 50 (31 to 69) for those who received 100 mg once daily. Active treatments were not different from each other. The mean (SD) plasma concentrations of montelukast were higher after the twice daily regimen (1.27 (0.81) microgram/ml) than after the once daily regimen (0.12 (0.09) microgram/ml); there was no correlation between the percentage protection against exercise-induced bronchoconstriction and plasma concentrations. After exercise urinary excretion of LTE4 increased significantly during placebo treatment (from 34.3 to 73.7 pg/mg creatinine; p < 0.05) but did not correlate with the extent of exercise-induced bronchoconstriction.
Montelukast protects similarly against exercise-induced bronchoconstriction between plasma concentrations of 0.12 and 1.27 micrograms/ml. The increase in the urinary excretion of LTE4 after exercise and the protection from exercise-induced bronchoconstriction with a cysteinyl leukotriene receptor antagonist provide further evidence of the role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.
开展了一项研究以确定孟鲁司特（一种新型强效半胱氨酰白三烯受体拮抗剂）是否能减轻运动诱发的支气管收缩。同时还研究了LTE4的尿排泄量与运动诱发的支气管收缩之间的关系。
纳入19例非吸烟哮喘患者，其一秒用力呼气容积（FEV1）≥预测值的65%，且运动后FEV1可重复性下降至少20%。受试者采用三周期随机双盲交叉设计，分别接受安慰剂、每晚一次100 mg孟鲁司特或每日两次50 mg孟鲁司特治疗，各治疗两天。在晚上，即每日一次给药后约20 - 24小时或每日两次给药后12小时，进行标准化运动激发试验。14例患者的数据可用于完整分析。
安慰剂组、每日一次给药组和每日两次给药组运动后FEV1的平均（标准差）最大下降百分比分别为29.6（16.0）、17.1（8.2）和14.0（9.4）。每日两次接受50 mg治疗组的平均（95%可信区间）保护率为37（15至59），每日一次接受100 mg治疗组为50（31至69）。活性治疗组之间无差异。每日两次给药方案后孟鲁司特的平均（标准差）血浆浓度（1.27（0.81）微克/毫升）高于每日一次给药方案后（0.12（0.09）微克/毫升）；预防运动诱发支气管收缩的保护率与血浆浓度之间无相关性。运动后，安慰剂治疗期间LTE 的尿排泄量显著增加（从34.3增至73.7 pg/mg肌酐；p < 0.05），但与运动诱发支气管收缩的程度无关。
孟鲁司特在血浆浓度为0.12至1.27微克/毫升之间对运动诱发的支气管收缩具有相似的保护作用。运动后LTE4尿排泄量的增加以及半胱氨酰白三烯受体拮抗剂对运动诱发支气管收缩的预防作用，进一步证明了白三烯在运动诱发支气管收缩发病机制中的作用。
