皮内物质P作为健康个体的挑战剂
Wouter Ten Voorde1,2, Chika Akinseye3, Ismahaan Abdisalaam1,4
1Centre for Human Drug Research, Leiden, The Netherlands.
Clinical and translational science
|August 7, 2023
概括
在健康志愿者中,物质P (SP) 皮肤内挑战显示了剂量依赖的小麦和火焰反应,在重复测试时没有转移效应. 这种SP挑战模型适用于未来针对皮肤炎症的药物开发研究.
科学领域:
- 药理学 药理学是指药理学的学科.
- 皮肤病学 皮肤病学
- 临床研究 临床研究
背景情况:
- 药理学挑战模型对于评估临床开发期间药物疗效至关重要.
- 皮内注射的物质P (SP) 是研究局部介质的潜在挑战剂,通过MRGPRX2受体引起和发烧反应.
- 现有的关于SP影响的数据缺乏完整的表征,并且在反复挑战后缺乏关于潜在的转移效应的信息.
研究的目的:
- 在健康参与者体内皮肤内SP挑战后,以剂量依赖的小麦粉和发烧反应为特征.
- 评估反复出现的SP挑战的潜在转移效应.
- 评估SP挑战模型对未来临床研究的适用性.
主要方法:
- 一个开放的,两部分的前性研究,涉及健康参与者的皮内SP挑战.
- 第1部分:确定最佳的SP剂量范围. 第二部分:使用皮肤内微透析 (IDM) 取皮肤样本的20名参与者的评估变异性.
- 测试的SP剂量为:5,15,50和150 pmol. 大约2周后进行了重复挑战.
主要成果:
- 在增加SP剂量 (5-150 pmol) 的情况下,观察到小麦和火焰反应的剂量依赖性增加.
- 当两个星期后重复SP挑战时,没有发现显著的转移效应.
- 皮内微透析 (IDM) 产生了低组胺水平,限制了释放组胺的时间表征.
- 实物P (SP) 耐受性良好,没有发现安全问题.
结论:
- 皮内SP挑战会引起不同的,剂量依赖的和发烧反应.
- SP挑战模型证明了可靠性,适合首次在人体上进行研究和评估皮肤炎症病的药物.
- 该模型可以帮助评估治疗慢性自发性疹和伪过敏反应等疾病的新疗法.
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