首页> 外文期刊>CPT: Pharmacometrics & Systems Pharmacology >Estimation of Equipotent Doses for Anti‐Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator
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Estimation of Equipotent Doses for Anti‐Inflammatory Effects of Prednisolone and AZD9567, an Oral Selective Nonsteroidal Glucocorticoid Receptor Modulator

机译:抗炎症剂量对泼尼松龙和AZD9567的抗炎作用的估算,口服选择性非甾体糖皮质激素受体调节剂

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摘要

AZD9567 is a potent and selective nonsteroidal oral glucocorticoid receptor modulator. It is developed as an anti‐inflammatory drug with improved safety profile compared with steroids like prednisolone. Throughout the clinical development of AZD9567, dose selection and data interpretation require a method for determining doses with the same anti‐inflammatory effect as prednisolone. Equipotent doses of AZD9567 and prednisolone were defined by the same average inhibition of TNFα release, a biomarker of anti‐inflammatory effect, measured in a lipopolysaccharide‐stimulated whole blood ex vivo assay. Based on pharmacokinetic‐pharmacodynamic models, TNFα dose‐response relationships for AZD9567 and prednisolone were established. A comparison of the dose‐response curves enabled estimation of an equipotency relationship. Specifically, 20?mg prednisolone was estimated to be equipotent to 40?mg AZD9567 (95% confidence interval: 29–54?mg). Static concentration‐response analyses showed that the relative potencies for inhibition of TNFα release of AZD9567 and prednisolone were well aligned with several other pro‐inflammatory cytokines.
机译:AZD9567是一种有效的选择性非甾体口服糖皮质激素受体调节剂。与泼尼松龙等类固醇相比,它是一种具有改善的安全性曲线的抗炎药。在整个AZD9567的临床开发中,剂量选择和数据解释需要一种用于测定具有与泼尼松龙相同的抗炎作用的剂量的方法。通过相同的平均抑制TNFα释放,抗炎作用的生物标志物,测定等电位剂量的AZD9567和泼尼松酮,以脂多糖刺激的全血exvivo测定来测量抗炎作用的生物标志物。基于药代动力学药物动力学模型,建立了AZD9567和泼尼松酮的TNFα剂量 - 反应关系。剂量响应曲线的比较使得估计等待性关系。具体而言,估计20μlmg泼尼松龙估计为40〜Mg AZD9567(95%置信区间:29-54μg)。静态浓度 - 反应分析表明,AZD9567和泼尼松龙TNFα释放的抑制相对型效率与几种其他促炎细胞因子相处得很好。

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