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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Validation of the human ozone challenge model as a tool for assessing anti-inflammatory drugs in early development.
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Validation of the human ozone challenge model as a tool for assessing anti-inflammatory drugs in early development.

机译：验证人类臭氧激发模型作为评估早期开发中抗炎药的工具。

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This study aimed to test the utility of the ozone challenge model for profiling novel compounds designed to reduce airway inflammation. The authors used a randomized, double-dummy, double-blind, placebo-controlled 3-period crossover design alternating single orally inhaled doses of fluticasone propionate (inhaled corticosteroids, 2 mg), oral prednisolone (oral corticosteroids, 50 mg), or matched placebo. At a 2-week interval, 18 healthy ozone responders (>10% increase in sputum neutrophils) underwent a 3-hour ozone (250 ppb)/intermittent exercise challenge starting 1 hour after drug treatment. Airway inflammation was assessed at 2 hours (breath condensate) and 3 hours (induced sputum) after ozone challenge. Compared to placebo, pretreatment with inhaled corticosteroids or oral corticosteroids resulted in a significant reduction (mean [95% confidence interval]) of sputum neutrophils by 62% (35%, 77%) and 64% (39%, 79%) and of sputum supernatant myeloperoxidase by 55% (41%, 66%) and 42% (25%, 56%), respectively. The authors conclude that an optimized ozone challenge model (including ozone responders and ensuring adequate drug levels during exposure) may be useful for testing novel anti-inflammatory compounds in early development.
机译：这项研究旨在测试臭氧激发模型用于分析旨在减轻气道炎症的新型化合物的实用性。作者使用了随机，双假人，双盲，安慰剂对照的3周期交叉设计，交替口服一次剂量的丙酸氟替卡松（吸入皮质类固醇，2 mg），泼尼松龙口服（口服皮质类固醇，50 mg）或相配安慰剂。每隔2周，对18名健康的臭氧反应者（痰中的中性粒细胞增加> 10％）进行3小时的臭氧治疗（250 ppb）/间歇性运动，开始于药物治疗后1小时。在臭氧激发后2小时（呼吸凝结物）和3小时（痰液诱导）评估气道炎症。与安慰剂相比，吸入皮质类固醇或口服皮质类固醇的预处理可显着减少痰中性粒细胞（平均[95％置信区间]）62％（35％，77％）和64％（39％，79％），痰上清髓过氧化物酶分别减少55％（41％，66％）和42％（25％，56％）。作者得出的结论是，优化的臭氧激发模型（包括臭氧应答剂并确保暴露期间具有足够的药物水平）可能有助于在早期开发中测试新型抗炎化合物。

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