Systems Toxicology Approach to Identifying Paracetamol Overdose.

Systems Toxicology Approach to Identifying Paracetamol Overdose.
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系统毒理学方法来鉴定扑热息痛过量。

DOI:
10.1002/psp4.12298
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发表时间:
2018-06
期刊:
CPT: pharmacometrics & systems pharmacology
影响因子:
--
通讯作者:
Webb SD
Webb SD
中科院分区:
其他
文献类型:
--
作者:
Mason CL;Leedale J;Tasoulis S;Jarman I;Antoine DJ;Webb SD

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扑热息痛(对乙酰氨基酚(APAP))是英国和美国最常用的镇痛药之一。然而,超过最大推荐剂量可能会导致严重的肝损伤甚至死亡。有前途的 APAP 毒性生物标志物被认为可以为目前使用的生物标志物增加价值,并且澄清这些生物标志物与肝损伤之间的功能关系将有助于临床实施改进的 APAP 毒性识别框架。目前用于定义 APAP 过量的框架高度依赖于摄入后的时间和初始剂量;通常是高度不可预测的信息。为了了解一组生物标志物与 APAP 剂量之间的关系,建立了药代动力学/药效 (PK/PD) APAP 模型。可视化和统计工具已用于预测初始 APAP 剂量和给药后的时间。此外,逻辑回归分析已应用于组织学数据,以提供肝损伤概率的预测。
Paracetamol (acetaminophen (APAP)) is one of the most commonly used analgesics in the United Kingdom and the United States. However, exceeding the maximum recommended dose can cause serious liver injury and even death. Promising APAP toxicity biomarkers are thought to add value to those used currently and clarification of the functional relationships between these biomarkers and liver injury would aid clinical implementation of an improved APAP toxicity identification framework. The framework currently used to define an APAP overdose is highly dependent upon time since ingestion and initial dose; information that is often highly unpredictable. A pharmacokinetic/pharmacodynamic (PK/PD) APAP model has been built in order to understand the relationships between a panel of biomarkers and APAP dose. Visualization and statistical tools have been used to predict initial APAP dose and time since administration. Additionally, logistic regression analysis has been applied to histology data to provide a prediction of the probability of liver injury.
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发表时间: 2013-08
期刊: HEPATOLOGY
影响因子: 13.5
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