A physiologically-based flow network model for hepatic drug elimination I: regular lattice lobule model
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RESEARCH
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A physiologically-based flow network model for hepatic drug elimination I: regular lattice lobule model Vahid Rezania1, Rebeccah Marsh2, Dennis Coombe3 and Jack Tuszynski2,4* * Correspondence: [email protected] 2 Department of Physics, University of Alberta, Edmonton, AB T6G 2J1, Canada 4 Department of Physics and Experimental Oncology, University of Alberta, Edmonton, AB T6G 2J1, Canada Full list of author information is available at the end of the article
Abstract We develop a physiologically-based lattice model for the transport and metabolism of drugs in the functional unit of the liver, called the lobule. In contrast to earlier studies, we have emphasized the dominant role of convection in well-vascularized tissue with a given structure. Estimates of convective, diffusive and reaction contributions are given. We have compared drug concentration levels observed exiting the lobule with their predicted detailed distribution inside the lobule, assuming that most often the former is accessible information while the latter is not.
Background The liver is the major site of biotransformation of endogenous and xenobiotic substances including drugs in the body. Its main role is to prevent accumulation of a wide range of chemical compounds in the blood by converting them into a form suitable for elimination. Such vital processes, however, can potentially damage liver tissue and hence its functionality. Examinations of hepatic clearance shows that substance extraction not only can be limited by damaged hepatocytes (liver cells) but also by the intrinsic (enzymatic) ability to eliminate the drug, by the resistance to drug transport from blood to eliminating tissue cells, and by the hepatic blood flow itself. Indeed, perturbations in the hepatic flow patterns e.g. through disease or aging can significantly alter the systemic clearance of these substances. As a result, a quantitative understanding between the liver performance and its structural integrity would be a great utility in the toxicology of newly developed drugs. To quantitatively assess these interacting processes, numerous models of hepatic clearance have been developed both in vitro and in silico, see an extensive review in [1]. Although in vitro liver models can be considered as the best alternative to analyze actual organ performance, their major shortcoming is to assume the liver as a homogeneous environment. It is known that metabolic functions, such as xenobiotic metabolism, amino acid conversion, cholesterol synthesis, oxidation, etc. are all zone specific. As a result, in vitro models are not necessarily well suited for studying and capturing the physiology of liver with hepatocyte morphology, property and functionality varying from point to point throughout of the organ. Because of this, there has been surge of interest among investigators in developing computational (in silico) © 2013 Rezania et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
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