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相关概念视频

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Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
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Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
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Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
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In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
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将肝芯片数据集成到制药决策过程中

Daniel Levner1, Lorna Ewart2

  • 1Chief Technology Officer, Emulate Inc, Boston, MA, USA.

Expert opinion on drug discovery
|September 13, 2023
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概括
此摘要是机器生成的。

肝芯片技术在临床试验中显示出减少药物诱导性肝损伤 (DILI) 失败的前景. 新的框架指导整合肝脏芯片数据,以更好地评估药物开发的安全性.

关键词:
药物诱导的肝损伤是药物诱导的肝脏芯片 - 肝脏芯片器官在芯片上的技术微生理系统的微生理系统患者安全 患者安全临床前安全评估 临床前安全评估监管指南 监管指南

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科学领域:

  • 生物技术是生物技术.
  • 药物开发 药物开发
  • 毒理学 毒理学 毒理学

背景情况:

  • 药物诱导性肝损伤 (DILI) 具有重大风险,导致大量药物戒断和临床试验失败.
  • 目前的临床前安全测试方法在准确预测DILI方面存在局限性.
  • 肝芯片技术为增强DILI预测提供了一种新的方法.

研究的目的:

  • 为将肝芯片技术纳入药物开发提供决策支持框架.
  • 引导药物开发商和监管机构利用肝芯片数据进行DILI风险评估.
  • 促进肝芯片技术在临床前安全测试中的采用.

主要方法:

  • 模拟肝脏芯片用于DILI预测的性能评估.
  • 开发一个使用量化肝芯片输出用于DILI严重性分析的框架.
  • 将肝芯片数据与传统动物试验结果集成在一起,用于做出"去"或"不去"的决定.

主要成果:

  • 肝芯片技术展示了准确的DILI预测的潜力.
  • 量化肝芯片数据使得对DILI严重性的细微风险分析成为可能.
  • 综合框架支持在临床前开发过程中的知情决策.

结论:

  • 肝芯片技术可以显著减少DILI相关的药物开发失败.
  • 采用肝芯片技术对于患者的安全至关重要.
  • 拟议的框架有助于将肝芯片数据纳入药物安全性评估过程.