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相关概念视频

Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

295
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...
295
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

273
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.
A recent model describes pravastatin's hepatobiliary excretion,...
273
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

1.1K
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
1.1K
Nonlinear Pharmacokinetics: Role of Transporters01:27

Nonlinear Pharmacokinetics: Role of Transporters

275
A drug's nonlinear kinetics can be influenced by a diverse range of transporter proteins that serve as crucial players in drug distribution. These transporters, found within cells, can enhance or reduce local drug concentrations by facilitating the influx or efflux of drugs. For instance, the expression of xenobiotic transporters can be influenced by factors such as age and gender, potentially impacting the linearity of drug response.
Polymorphisms occurring in drug transporters can alter...
275
Factors Affecting Renal Clearance: Drug's Physicochemical Properties and Plasma Levels01:31

Factors Affecting Renal Clearance: Drug's Physicochemical Properties and Plasma Levels

578
Renal clearance of a drug is influenced by various factors, including its physicochemical properties and plasma levels. These factors play a significant role in determining how efficiently the kidneys eliminate a drug.
One important factor is the drug's molecular size. The kidneys readily excrete smaller molecules below 300 Daltons (Da). On the other hand, molecules weighing between 300 and 500 Da are excreted through both urine and bile. Larger molecules above 500 Da tend to be excreted...
578
Renal Drug Clearance: Overview01:06

Renal Drug Clearance: Overview

663
Renal clearance is a crucial parameter in pharmacokinetics that quantifies the rate at which the kidneys excrete a drug. It represents a constant fraction of the central volume of distribution containing the drug that the kidney eliminates per unit of time.
Renal clearance can be calculated using different methods. One approach is to divide the urinary drug excretion rate by the plasma drug concentration. This method directly measures renal clearance, indicating the kidneys' efficiency in...
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相关实验视频

Updated: Jan 14, 2026

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
18:57

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Published on: October 17, 2013

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净流量而不是定向速率:重新评估脏和肝脏清除的体外和体外载体表征.

Leslie Z Benet1, Jasleen K Sodhi2,3

  • 1Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, San Francisco, CA, 94143-0912, USA. Leslie.Benet@ucsf.edu.

The AAPS journal
|October 23, 2025
PubMed
概括

这项研究挑战了扩展清除概念 (ECC),表明肝脏清除取决于净输送活性,而不仅仅是流入. 我们的新框架提供了更准确的药物处置和输送器角色的解释.

关键词:
肝脏清除时间基尔赫霍夫的定律 基尔赫霍夫的定律净流入量 净流入量 净流入量通过脏清除.运输商 运输商 运输商

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An In Vivo Method for Evaluating the Gut-Blood Barrier and Liver Metabolism of Microbiota Products
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相关实验视频

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An In Vivo Method for Evaluating the Gut-Blood Barrier and Liver Metabolism of Microbiota Products
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科学领域:

  • 药理动力学 药理动力学
  • 药物新陈代谢 药物新陈代谢
  • 基于生理学的药理动力学建模

背景情况:

  • 扩展清除概念 (ECC) 经常假设肝脏吸收清除仅限于运输体流入的速度.
  • 目前的解释可能过于简化了复杂的药物处置机制.
  • 生理学基础的药理动力学 (PBPK) 分析和实验数据尚未最终验证ECC框架.

研究的目的:

  • 质疑肝脏吸收清除仅取决于输送体流入的假设.
  • 开发一个更强大的和机理上一致的框架来解释和肝清除.
  • 突出ECC和当前用于评估输送器功能的体外检测方法的局限性.

主要方法:

  • 通过使用与基尔霍夫定律类似的原则,审查和肝清除的推导.
  • 包括器官血液流动,输送器活动和全身药物输送.
  • 分析了流入和流出间距的净差异,作为输送器参与的决定因素.

主要成果:

  • 肝脏清除值数据通过一个框架充分解释,强调了流入和流出清除值之间的净差异.
  • 突出了ECC框架在捕捉毒品处置的所有机制元素方面的局限性.
  • 目前用于确定肝脏流入和流出清除的体外方法可能无法准确量化定向运输.

结论:

  • 流入和流出清除之间的净差异,而不是单独的流入,是输送器参与肝脏药物处置的关键决定因素.
  • 一个新的导出提供了一个更有机理的方法来解释脏和肝脏清除.
  • 虽然PBPK和ECC对于预测是有用的,但基于模型的拟合并不等同于机械验证.