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

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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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Model Approaches for Pharmacokinetic Data: Physiological Models01:15

Model Approaches for Pharmacokinetic Data: Physiological Models

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Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...
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Physiological Pharmacokinetic Models: Assumption with Protein Binding01:13

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Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
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Nonlinear Pharmacokinetics: Role of Transporters01:27

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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.
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Physiological Pharmacokinetic Models: Blood Flow-Limited Versus Diffusion-Limited Models00:57

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Physiological pharmacokinetic models, often called flow-limited or perfusion models, typically assume a swift drug distribution between tissue and venous blood, creating a rapid drug equilibrium. This premise is based on the idea that drug diffusion is extremely fast, and the cell membrane presents no barrier to drug permeation. In this scenario, where no drug binding occurs, the drug concentration in the tissue equals that of the venous blood leaving the tissue. This greatly simplifies the...
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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.
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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
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通过使用生理学基础的药理动力学建模来评估载体介导的里法-林佐利德相互作用.

Hoang Dat Nguyen1, Vinh Hoa Pham2, Richard M Hoglund3,4

  • 1Master of Science Program in Biopharmaceutical Sciences, Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

British journal of clinical pharmacology
|January 27, 2026
PubMed
概括
此摘要是机器生成的。

结合ATP的磁带亚家族B成员1 (ABCB1) 载体主要驱动着里法和线索立德之间的药物相互作用. 与标准剂量相比,高剂量的利法并不显著改变线索利德的暴露.

关键词:
药物 药物相互作用在线zolidlid是什么意思基于生理学的药物动力学模型.这就是为什么Rifampin是Rifampin.运输商 运输商 运输商 运输商

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科学领域:

  • 药理动力学和药物新陈代谢
  • 计算机生物学和建模
  • 传染病药理学 传染病药理学

背景情况:

  • 药物相互作用 (DDI) 涉及利芬和线索利德可以改变线索利德的疗效和安全性.
  • 了解ABCB1和ABCG2等特定载体的作用,对于预测和管理这些相互作用至关重要.
  • 基于生理学的药理动力学 (PBPK) 建模提供了一种定量方法来研究复杂的DDI.

研究的目的:

  • 开发和验证linezolid的PBPK模型.
  • 量化评估ABCB1和ABCG2载体对利法-线化物DDI的贡献.
  • 预测高剂量里法胺对线化物药理动力学 (PK) 的影响.

主要方法:

  • 用临床PK数据构建和验证了linezolid的PBPK模型.
  • 我们使用了一种PK-SIM PBPK模型来对抗利法,该模型包含了ABCB1和ABCG2输送活性.
  • 在PBPK模拟中预测了与里法胺联合使用时的linezolid PK,包括高剂量场景.

主要成果:

  • 在多项临床研究中,linezolid PBPK模型表现出良好的预测性能.
  • PBPK模拟表明,ABCB1在里法-林佐利德DDI中比ABCG2发挥更重要的作用.
  • 预测的标准剂量里法的DDI比率与观察到的临床数据密切匹配.
  • 增加里法的剂量并没有实质性地改变linezolid的暴露.

结论:

  • 鉴定出ABCB1是中介Rifampin和linezolid之间的DDI的主要载体.
  • 高剂量里法胺对线化物暴露的DDI影响与标准剂量里法胺的影响相当.
  • PBPK建模为预测传送器介导的DDI提供了有价值的工具.