Gastrointestinal tract density

Because the amounts and density of these transporters vary along the gastrointestinal tract, it is necessary to introduce a correction factor for the varying transport rates in the different luminal and enterocyte compartments. Due to the lack of experimental data for the regional distribution, and Michaelis-Menten constants for each drug in Table 18.2, we fitted an intrinsic (concentration-independent) transport rate for each drug to closely approximate the experimental %HIA. This... 

The oral cavity and the lower gastrointestinal tract are densely colonized by bacteria with counts exceeding 109 colony-forming units (CFU)/ml, whereas the density in the stomach and proximal small bowel is normally below 105 CFU/ml (fig. 1). Bacterial density increases through... 

Fig-1. The density of bacteria along the gastrointestinal tract of man is shown schematically based on data from references 1-5 in the text. Density is given by logio CFU/ml of luminal contents in the fasting state. TBC = Total bacterial count. 

In this section several recently published studies on the interaction of nonionic surfactants with a variety of biological systems, including enzymes, bacteria, erythrocytes, leukocytes, membrane proteins, low density lipoproteins and membranes controlling absorption from the gastrointestinal tract, nasal and rectal cavities, will be assessed. This is a selective account, work having been reviewed that throws light on structure-activity relationships and on mechanisms of surfactant action. 

The 5-HT3 receptor is the only monoamine neurotransmitter receptor that functions as a lig-and-gated ion channel, controlling the flux of Na-i- and K+ ions. 5-HT3 receptors are located on parasympathetic nerve terminals in the gastrointestinal tract, and high densities are found in areas of the brain associated with the emetic response, such as the area postrema. The antiemetic effects of 5-HT3 antagonists, such as ondansetron, result from actions at these sites. 5-HT3 receptors in the dorsal horn of the spinal cord have been implicated in nociception and development of new 5-HT3 receptor-related compounds may have potential as non-opioid, non-addictive analgesics. 

He, P. Davis, S.S. Ihum, L. Chitosan microspheres prepared by spray drying. Int. J. Pharm. 1999,187, 53-65. Rechgaard, H. Beggsen, S. Distribution of pellets in the gastrointestinal tract. The influence of transit time exerted by density or diameter of pallets. J. Pharm. Pharmacol. 1978, 30, 690. 

FIGURE 3.7 Approximate concentrations of bacteria in various regions of the gastrointestinal tract. The density of bacteria in the human stomach and small intestine is relatively low compared with that in the large intestine, unlike other species shown. The human stomach contains about 100 bacteria per g contents, whereas the large intestine contains about one billion per gram. For comparison, a sample of pure bacterial cells contains about one trillion cells per gram. (Redrawn with permission from Rowland, 1988.)... 

Pharmaceuticals that require metal ions for their specific activity and in which the metals have a very active role are fewer in number but hold far greater fascination. The metal ion may be present because it has the ability, coupled with its coordination chemistry properties, to direct covalent bonds or because it is a source of positive charge density or because the metal is able to form specific bonds to an active site in the biochemistry of the diseased organ. Furthermore, it is frequently necessary to raise the concentration of the total amount of the trace metal present in tissue in order to allay the symptoms of a deficiency condition. This means that the metal ion has to be made bioavailable such that it can pass from the gastrointestinal tract into the bloodstream. 

Somatostatin is a neuroregulatory peptide secreted by the hypothalamus. Human somatostatin receptors (ssts) are expressed in the brain, anterior pituitary gland, pancreas, thyroid gland, and in the mucosa of the gastrointestinal tract (Hofland and Lamberts 1997 Patel 1999). Tumors arising from sst-positive cells in these organs contain a high density of ssts (Hofland et al. 2003 Lamberts et al. 1991 Reubi 1996). 

Despite the fact that a plethora of dietary factors could, and will, affect the absorption characteristics of phytochemicals, this area has not been systematically explored. One reason might be the complexity of dietary factors and their interactions that could affect absorption. A nonexhaustive list would include the volume and composition of the food consumed, pH, caloric density, viscosity, nutrients (carbohydrates, protein, fat, fibers), alcohol, caffeine, and the presence of other phytochemicals. Such dietary factors affect the functional status, motility, and acidity of the gastrointestinal tract in a complex manner and modify the physicochemical properties, formulation, and dissolution characteristics of the compound of interest. Calcium in dairy products, for example, has the potential to chelate tetracyclines and fluoroquinolones and, thereby, reduce their bioavailability and biological activity [31]. 

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