Intestinal computational models

Bergstrom, C. A. S. Computational models to predict aqueous drug solubility, permeability and intestinal absorption. Exp. Opin. Drug Metab. Toxicol. 2005, 1, 513-527. 

Fluxes of iron from the plasma towards BM and other tissues can be quantified by ferrokinetic studies, using 59Fe and sophisticated computer models (Ricketts et ah, 1975 Ricketts and Cavill, 1978 Barosi et ah, 1978 Stefanelli et ah, 1980). Plasma iron turnover (PIT), erythroid iron turnover (EIT), non-erythroid iron turnover (NEIT), marrow iron turnover (MIT), and tissue iron turnover (TIT) could be calculated in many disorders of iron metabolism and in all kinds of anaemias. Iron is rapidly cleared from the plasma in iron deficiency and in haemolytic anaemias. If more iron is needed for erythropoiesis, more transferrin receptors (TfR) are expressed on erythroblasts, resulting in an increased flux of iron from intestinal mucosal cells towards the plasma. In haemolytic anaemias MPS, and subsequently hepatocytes, are overloaded. In hereditary haemochromatosis too much iron is absorbed by an intrinsic defect of gut mucosal cells. As this iron is not needed for erythropoiesis,... 

Computational models for blood-brain-barrier penetration have been well reviewed in detail by Clark [36]. Penetration of the blood-brain-barrier (BBB) via passive diffusion is dependent upon the hydrophilicity and lipophilicity of a molecule. However, the BBB is a thicker, more lipophilic membrane than the intestinal membrane. Kelder et al. [37] showed that very few of 776 orally administered CNS drugs had PSA >90, while a substantial fraction of 1590 orally administered non-CNS had PSA >90. These results demonstrate the poor BBB penetration by hydrophilic molecules. 

Klopman G, Stefan LR, Saiakhov RD (2002) ADME evaluation 2. A computer model for the prediction of intestinal absorption in humans. Eur. J. Pharm. Sci. 17 253-263. 

In Silico ADME Modeling 3 Computational Models to Predict Human Intestinal Absorption Using Sphere Exclusion and kNN QSARMethods. QSAR Combinatorial Science, 5, 653-668. 

The lack of generally applicable direct methods to measure intestinal metabolism in humans (see Section 12.4.1) emphasizes the need for reliable computational models to differentiate intestinal metabolism from hepatic first-pass metabolism. Historically, the well-stirred (venous equilibrium) model has been adapted to the gut [1, 29] and used for these predictions according to Equation 12.7 ... 

Gunturi, S.B. and Narayanan, R. (2007) In silico ADME modeling 3 computational models to predict human intestinal absorption using sphere exclusion... 

During the past 10 years starting with the publications of Lipinski and coworkers [1] and Palm and coworkers [2], a considerable amount of research has been performed to develop predictive computational models for intestinal absorption in humans. The purpose of these investigations has been to develop computationally fast and accurate models for in silico electronic screening of large virtual compound libraries. 

Computational models to predict human intestinal absorption using sphere exclusion and kNN QSAR methods... 

Swaan PW, Szoka FC, Jr. and Oie S. Molecular modeling of the intestinal bile acid carrier a comparative molecular field analysis study. J Comput Aided Mol Des 1997 11 581-8. 

Figure 22.1 A. Schema for a physiologically based pharmacokinetic model incorporating absorption in the stomach and intestines and distribntion to various tissues. B. Each organ or tissue type includes representation of perfusion (Q) and drug concentrations entering and leaving the tissue. Fluxes are computed by the product of an appropriate rate law, and permeable surface area accounts for the affinity (e.g., lipophilic drugs absorbing more readily into adipose tissue). Clearance is computed for each tissue based on physiology and is often assumed to be zero for tissues other than the gut, the liver, and the kidneys.

Stenberg, P., Norinder, U., Luthman, K., Artursson, P. Experimental and computational screening models for the prediction of intestinal drug absorption. 

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