Zileuton: clinical implications of 5-Lipoxygenase inhibition in severe airway disease
Zileuton: clinical implications of 5-Lipoxygenase inhibition in severe airway disease
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DOI：
10.1111/j.1742-1241.2007.01320.x
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发表时间：
2007-04-01
影响因子：
2.6
通讯作者：
Cairns, C. B.
中科院分区：
文献类型：
--
作者：
Berger, W.;De Chandt, M. T. M.;Cairns, C. B.
5-脂氧合酶途径导致白三烯的形成，包括白三烯B-4（LTB 4）、5-氧代-6 E，8 Z，11 Z，14 Z-二十碳四烯酸和半胱氨酰白三烯（LTC 4、LTD 4和LTE 4），并激活所有四种白三烯受体BLT 1、BLT 2、cysLT（1）和cysLT（2）。齐留通是唯一市售的5-脂氧合酶途径抑制剂。在许多临床试验中，齐留通已被证明可以改善气道功能和炎症，哮喘症状控制和哮喘患者的生活质量。考虑到白三烯在气道炎症中的重要作用，齐留通为慢性持续性哮喘的治疗提供了额外的选择，特别是那些病情更严重的哮喘患者。此外，zileuton在许多其他疾病中也显示出了希望，包括上呼吸道炎症、皮肤病和慢性阻塞性肺病。新制剂的开发，包括用于b.i.d.的控释片剂。用于急性哮喘恶化的给药和静脉内制剂可增强临床效用并扩展治疗适应症。
The 5-Lipoxygenase pathway results in the formation of leukotrienes, including leukotriene B-4 (LTB4), 5-oxo-6E,8Z,11Z,14Z-eicosatetranoic acid and the cysteinyl leukotrienes (LTC4, LTD4 and LTE4) and activates all four leukotriene receptors, BLT1, BLT2, cysLT(1) and cysLT(2). Zileuton is the only commercially available inhibitor of the 5-Lipoxygenase pathway. In a number of clinical trials, zileuton has been shown to improve airway function and inflammation, asthma symptom control and quality of life in asthmatics. Given the important role that leukotrienes play in airway inflammation, zileuton provides an additional therapeutic option in the management of chronic, persistent asthma, particularly those asthmatics with more severe disease. In addition, zileuton has shown promise in a number of other conditions, including upper airway inflammatory conditions, dermatological disease and chronic obstructive pulmonary disease. The development of new formulations, including a controlled release tablet formulation for b.i.d. dosing and an intravenous preparation for acute asthma exacerbations may enhance clinical utility and expand therapeutic indications.