Impact of a soluble phospholipase A2 inhibitor on inhaled allergen challenge in subjects with asthma
Impact of a soluble phospholipase A2 inhibitor on inhaled allergen challenge in subjects with asthma
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DOI：
10.1081/jas-200044748
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发表时间：
2005-02-01
影响因子：
1.9
通讯作者：
Sides, GD
中科院分区：
文献类型：
--
作者：
Bowton, DL;Dmitrienko, AA;Sides, GD
分泌型磷脂酶A（2）（sPLA（2））在哮喘中的可能作用包括从细胞膜释放花生四烯酸、产生溶血磷脂、sPLA（2）介导的cPLA（2）活化并增加白三烯产生和表面活性剂降解。LY 333013是sPLA的有效抑制剂（2）。本研究检查了两种剂量的LY 333013与安慰剂对特应性哮喘患者吸入过敏原激发后过敏原诱导的支气管收缩的影响。50例受试者被随机分配接受治疗，40例受试者完成研究。采用双盲、安慰剂对照、随机顺序、交叉研究设计。LY 333013对吸入过敏原激发后早期（0-3小时）（AUC（早期））和晚期（3-8小时）（AUC（晚期））FEV 1反应曲线下面积的主要结局变量无影响。未观察到显著的药物相关不良反应。对吸入过敏原激发的反应是可再现的，并证实了该技术作为筛选化合物用于哮喘患者进一步测试的模型的实用性。
The possible roles of secretory phospholipases A(2) (sPLA(2)) in asthma include the release of arachidonic acid from cellular membranes, generation of lysophospholipids, sPLA(2)-mediated activation of cPLA(2) with increased leukotriene production, and surfactant degradation. LY333013 is a potent inhibitor of sPLA(2). This study examined the impact of two doses of LY333013 vs. placebo on allergen-induced bronchoconstriction following inhaled allergen challenge in atopic asthmatics. Fifty subjects were randomly assigned to treatment, and 40 subjects completed the study. A double-blind, placebo-controlled, random order, crossover study design was used. LY333013 had no impact on the primary outcome variables of the areas under the FEV1 response curve early (0-3 hours) (AUC(early)) and late (3-8 hours) (AUC(late)) following inhaled allergen challenge. No significant drug-related adverse effects were observed. The response to inhaled allergen challenge was reproducible and confirms the utility of this technique as a model in which to screen compounds for further testing in asthmatic patients.