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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Variability of histamine pharmacodynamic response in children with allergic rhinitis
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Variability of histamine pharmacodynamic response in children with allergic rhinitis

机译：过敏性鼻炎患儿组胺药效学反应的变化

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摘要

Histamine iontophoresis with laser Doppler monitoring (HILD) is a robust and dynamic surrogate for histamine microvasculature response. We characterized histamine pharmacodynamics in children using HILD. HILD was performed in 54 children with allergic rhinitis. A non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD model was used to provide estimates for area under the effect curve (AUEC), maximal response over baseline (EffmaxNT), and time of EffmaxNT (Tmax). Data were placed in sub-groups by visualization of time vs. response relationships. ANOVA and regression analyses were used for sub-group comparisons. Three histamine response phenotypes were identified. One group demonstrated a hyper-responsive phenotype (higher Tmax, EffmaxNt and AUEC, P > .01). AUEC and EffmaxNT were more strongly associated in this group (r2 = 0.86) than the entire cohort (r2 = 0.64). These data demonstrate a hyper-responsive histamine phenotype via HILD. This finding is important to future pharmacologic studies of antihistamines.
机译：具有激光多普勒监测（HILD）的组胺离子电渗疗法是对组胺微脉管系统反应的一种强大而动态的替代方法。我们对使用HILD的儿童进行了组胺药效学研究。 HILD在54例过敏性鼻炎患儿中进行。使用带有链接效应PK / PD模型的非隔离分析和非线性混合效应模型来提供效应曲线下面积（AUEC），基线最大响应（EffmaxNT）和EffmaxNT时间（Tmax）的估计值）。通过时间与响应关系的可视化将数据放在子组中。方差分析和回归分析用于亚组比较。确定了三种组胺反应表型。一组表现出高反应性表型（较高的Tmax，EffmaxNt和AUEC，P> .01）。与整个队列（r2 = 0.64）相比，该组中的AUEC和EffmaxNT具有更强的关联性（r2 = 0.86）。这些数据证明了通过HILD的高反应性组胺表型。该发现对于抗组胺药的未来药理研究很重要。

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