Gastrointestinal tract physiology

The ruminant animal differs significantly from monogastric animals, such as humans, rodents, and swine, in gastrointestinal tract physiology and digestion. In particular, ruminant animals have a rumen, or pregastric... 

Toxicity. Fluoroborates are excreted mostly in the urine (22). Sodium fluoroborate is absorbed almost completely into the human bloodstream and over a 14-d experiment all of the NaBF ingested was found in the urine. Although the fluoride ion is covalently bound to boron, the rate of absorption of the physiologically inert BF from the gastrointestinal tract of rats exceeds that of the physiologically active simple fluorides (23). 

PARs are coupled to multiple G-proteins and mediate a number of well-defined cellular responses via classical second messenger and kinase pathways. PARs are differentially expressed in cells of the vasculature as well in the brain, lung, gastrointestinal tract, skin as well as other highly vascularised tissues and evidence suggests distinct physiological functions and roles in disease states [2]. 

Hartshome, D.J. (1987). Biochemistry of the contractile process in smooth muscle. In Physiology of the Gastrointestinal Tract. 2nd Edition (Johnson. L.R. ed.), pp. 423-482, Raven Press, New York. Hille, B. (1992). Ionic Channels of Excitable Membranes. 2nd edn., Sinauer Associates, Sunderland, MA. 

Irritable bowel syndrome (IBS) is a disorder of the gastrointestinal tract that interferes with the normal functions of the colon. At various points in the past, IBS has been referred to as mucous colitis, spastic colon, irritable colon, or nervous stomach. IBS is generally described as afunctional disorder rather than a disease per se. A functional disorder involves symptoms that cannot be attributed to a specific injury, infection, or other physical problem. A functional disorder occurs because of altered physiologic processes rather than structural or biochemical defects and may be subject to nervous system influence. IBS is associated with frequent fluctuation in symptoms, loss of productivity, and decreased quality of life. Although IBS has been referred to as functional bowel disease, true functional bowel disease may be more indicative of widespread gastrointestinal involvement including (but not limited to) the colon. 

Prostaglandins play critical roles in a number of physiological processes. These molecules regulate blood flow to organs, stimulate secretion of protective mucosal linings in the gastrointestinal tract, participate in the initiation of platelet aggrega-... 

Stirred tank models have been widely used in pharmaceutical research. They form the basis of the compartmental models of traditional and physiological pharmacokinetics and have also been used to describe drug bioconversion in the liver [1,2], drug absorption from the gastrointestinal tract [3], and the production of recombinant proteins in continuous flow fermenters [4], In this book, a more detailed development of stirred tank models can be found in Chapter 3, in which pharmacokinetic models are discussed by Dr. James Gallo. The conceptual and mathematical simplicity of stirred tank models ensures their continued use in pharmacokinetics and in other systems of pharmaceutical interest in which spatially uniform concentrations exist or can be assumed. 

JL Madara, JS Trier. Functional morphology of the mucosa of the small intestine. In LR Johnson, ed. Physiology of the Gastrointestinal Tract. 2nd ed. New York Raven, 1994. 

LR Johnson. Physiology of the gastrointestinal tract. Raven Press, New York, NY 1994. 

Tso, P. 1981. Intestinal lipid absorption. In Physiology of the Gastrointestinal Tract, ed. L. R. Johanson, pp. 1867-1907, New York Raven Press. 

Steroid hormones are produced by the adrenal cortex, testes, ovaries, and placenta. Synthesized from cholesterol, these hormones are lipid soluble therefore, they cross cell membranes readily and bind to receptors found intracellularly. However, because their lipid solubility renders them insoluble in blood, these hormones are transported in the blood bound to proteins. Furthermore, steroid hormones are not typically preformed and stored for future use within the endocrine gland. Because they are lipid soluble, they could diffuse out of the cells and physiological regulation of their release would not be possible. Finally, steroid hormones are absorbed easily by the gastrointestinal tract and therefore may be administered orally. 

A summary of how physiological factors affect the dissolution rate is given in Table 21.2. The effective surface area will be affected by the wetting properties of the bile acids and other surface-active agents in the gastrointestinal tract. The dif-fusivity of a drug molecule in the intestinal juice will be altered by changes in viscosity that are induced, for instance, by meal components. An increased dissolution rate could be obtained at more intense intestinal motility patterns or increased... 

Extensions of BCS beyond the oral IR area has also been suggested, for example to apply BCS in the extended-release area. However, this will provide a major challenge since the release from different formulations will interact in different ways with in vitro test conditions and the physiological milieu in the gastrointestinal tract. For example, the plasma concentration-time profile differed for two felodipine ER tablets for which very similar in vitro profiles had been obtained, despite the fact that both tablets were of the hydrophilic matrix type based on cellulose derivates [70], This misleading result in vitro was due to interactions between the gel strength of the matrix and components in the dissolution test medium of no in vivo relevance. The situation for ER formulations would be further complicated by the need to predict potential food effects on the drug release in vivo. 

The second situation when IVIVC is not likely for class II drugs is where the absorption is limited by the saturation solubility in the gastrointestinal tract rather than the dissolution rate, as discussed in more detail above. In this situation, the drug concentration in the gastrointestinal tract will be close to the saturation solubility, and changes of the dissolution rate will not affect the plasma concentrationtime profile and in vivo bioavailability. Standard in vitro dissolution tests are carried out under sink conditions , i.e., at concentrations well below the saturation solubility. Thus, only effects related to dissolution rate can be predicted in vitro. If more physiologically relevant dissolution media are used, which do not necessarily provide sink conditions , the possibility for IVIVC could be improved, as has been indicated by the results of recent studies using simulated intestinal medium [76],... 

Eve, I. S. (1966). A review of the physiology of the gastrointestinal tract in relation to radiation doses from radioactive materials, Health Phys.-12, 131. 

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