Physiologically based pharmacokinetic models for the transport of trichloroethylene in adipose tissue
Physiologically based pharmacokinetic models for the transport of trichloroethylene in adipose tissue
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DOI：
10.1006/bulm.2001.0268
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发表时间：
2002-01-01
影响因子：
3.5
通讯作者：
Potter, LK
中科院分区：
文献类型：
--
作者：
Albanese, RA;Banks, HT;Potter, LK
在本文中，我们提出了三种基于生理学的药代动力学 (PBPK) 模型，用于三氯乙烯 (TCE) 的全身转运，重点关注脂肪或脂肪组织。三氯乙烯是一种广泛存在的环境污染物，已被证明会对动物和人类产生毒性作用。 TCE的一个关键特征是其在脂肪组织中积累的倾向，这对TCE的整体系统分布有重大影响。这里我们使用PBPK模型来预测TCE在包括脂肪组织在内的各种组织和器官中的动态。第一个模型使用脂肪组织的标准“灌注限制”隔室模型，而第二个模型使用“扩散限制”模型来描述通过脂肪组织的运输。这两种 ODE 模型都基于“充分混合”和快速平衡假设，并且没有考虑脂肪组织的特定且很大程度上异质的生理学。我们讨论的第三个模型是具有脂肪组织轴向弥散型模型的 PBPK 混合模型。这种基于 PDE 的模型旨在捕获脂肪组织的关键生理异质性，包括广泛变化的脂肪细胞大小、脂质分布和血流特性。模型模拟演示。 (C) 2002 年数学生物学学会。
In this paper we present three physiologically based pharmacokinetic (PBPK) models for the systemic transport of trichloroethylene (TCE), with a focus on the adipose, or fat tissue. TCE is a widespread environmental contaminant, and has been shown to produce toxic effects in both animals and humans. A key characteristic of TCE is its tendency to accumulate in fat tissue, which has a major impact on the overall systemic disposition of TCE.Here we use PBPK models to predict the dynamics of TCE in the various tissues and organs, including the adipose tissue. The first model utilizes the standard 'perfusion-limited' compartmental model for the fat tissue, while the second model uses a 'diffusion-limited' model to describe the transport through the adipose tissue. Both of these ODE models are based on 'well-mixed' and rapid equilibrium assumptions, and do not take into account the specific and largely heterogeneous physiology of adipose tissue.The third model we discuss is a PBPK hybrid model with an axial-dispersion type model for the adipose tissue. This PDE-based model is designed to capture key physiological heterogeneities of fat tissue, including widely varying fat cell sizes, lipid distribution, and blood flow properties. Model simulations demonstrate. (C) 2002 Society for Mathematical Biology.