Intestine, small

In the small intestine, contact time with the absorptive epithelium is limited, and a small intestinal transit time (SITT) of 3.5-4.5 hr is typical in healthy volunteers. The Holy Grail of drug delivery would be to discover a mechanism that 

Infusion of fat into the ileum has been shown to cause a lengthening of the SITT—a phenomenon known as the ileal brake (27,28). However, the effect is generally modest (causing a delay of 30-60 min) and attempts to exploit this mechanism in drug delivery have had limited success. Dobson et al. (29,30) studied the effect of co-administered oleic acid on the small intestinal transit of non-disintegrating tablets. They showed a delay in SITT in over half of all cases, and a doubling of SITT in some instances, but in the other cases SITT was either unaffected or even reduced. Lin et al. (31) have also showed slowed GI transit in patients with chronic diarrhea by administration of emulsions containing 0, 1.6, and 3.2 g of oleic acid. Small intestinal transit in normal subjects was measured at 102 11 min, while the transit times in the patients treated with the three emulsions were, respectively, 29 3, 57 5 and 83 5 min. 

11 Transport of bile and pancreatic juice to small intestine 

Bile is secreted by the liver, stored in the gallbladder, and used in the small intestine. It is transported toward the small intestine by the hepatic duct (from the liver) and the cystic duct (from the gallbladder), which join to form the common bile duct. Pancreatic juice is transported toward the small intestine by the pancreatic duct. The common bile duct and the pancreatic duct join to form the hepatopancreatic ampulla, which empties into the duodenum. The entrance to the duodenum is surrounded by the Sphincter of Oddi. This sphincter is closed between meals in order to prevent bile and pancreatic juice from entering the small intestine it relaxes in response to the intestinal hormone cholecystokinin, thus allowing biliary and pancreatic secretions to flow into the duodenum. 

The small intestine is the longest ( 6 m) and most convoluted organ in the digestive system. It is divided into three segments  

Most digestion and absorption take place in the small intestine, the mucosa of which is well adapted for these functions with certain anatomical modifications  

The plicae circulares, or circular folds, form internal rings around the circumference of the small intestine that are found along the length of the small intestine. They are formed from inward foldings of the mucosal and submucosal layers of the intestinal wall. The plicae circulares are particularly well developed in the duodenum and jejunum and increase the absorptive surface area of the mucosa about threefold. Each plica is covered with millions of smaller projections of mucosa referred to as villi. Two types of epithelial cells cover the villi  

Keywords Oral absorption Bioavailability Models of small intestine Intestinal permeability Intestinal perfusion techniques Intestinal versus hepatic first-pass metabolism 

Understanding the factors influencing drug absorption and in particular predicting these values on the basis of pre-clinical in vitro and in situ experiments remains crucial to bringing safe and effective drugs to the market [3], 

There are a variety of methods available for studying intestinal absorption as will be outlined in this chapter. Given the complexity of the absorption process, each individual model will differ in terms of merits and inherent assumptions. The key advantage of in situ/in vivo models will be the intact blood supply and 

Physiochemical factors of drug substances Physiological factors of GIT Dosage form and formulation factors 

Solubility Stomach emptying rate Dissolution rate 

The rate of passage of food into the duodenum depends on the type of food and on the osmotic pressure it exerts in the duodenum. Food rich in fat moves most slowly, food rich in carbohydrate moves most rapidly, and food rich in protein moves at an intermediate rate. Hyperosmolality decreases gastric emptying via duodenal osmoreceptors. Some GI hormones also inhibit gastric motility and secretion. 

Endocrine cells are distributed throughout the small intestine and other sections of the GI tract. About 20 different cell types have been identified. Some, easily identifiable by their staining characteristics, are argentaffin or ente-rochromaffin cells containing 5-hydroxytryptophan, the precursor of serotonin (Chapter 17). Neoplastic transformation of these cells leads to excessive production and secretion of serotonin, which causes diarrhea, flushing, and bronchoconstriction carcinoid syndrome). Other types of cells lack 5-hydroxytryptophan but take up amine precursors (e.g., amino acids) to synthesize and store biologically active peptides (e.g., hormones). 

Digestion in the small intestine requires the biliary and pancreatic secretions that are emptied into the duodenum (usually at a common site). 

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Invertase (sucrasc) small intestine, yeast sucrose glucose and fructose 6 2 (gut) 4 8 (yeast)... 

As we have seen in this chapter steroids have a number of functions in human physiology Cholesterol is a component part of cell mem branes and is found in large amounts in the brain Derivatives of cholic acid assist the digestion of fats in the small intestine Cortisone and its derivatives are involved in maintaining the electrolyte balance in body fluids The sex hormones responsible for mascu line and feminine characteristics as well as numerous aspects of pregnancy from conception to birth are steroids... 

Lipids present in the diet may become rancid. When fed at high (>4-6%) levels, Hpids may decrease diet acceptabiUty, increase handling problems, result in poor pellet quaUty, cause diarrhea, reduce feed intake, and decrease fiber digestion in the mmen (5). To alleviate the fiber digestion problem, calcium soaps or prilled free fatty acids have been developed to escape mminal fermentation. These fatty acids then are available for absorption from the small intestine (5). Feeding whole oilseeds also has alleviated some of the problems caused by feeding Hpids. A detailed discussion of Hpid metaboHsm by mminants can be found (16). 

Vitamins A, D, and E are required by mminants and, therefore, their supplementation is sometimes necessary. Vitamin A [68-26-8] is important in maintaining proper vision, maintenance and growth of squamous epitheHal ceUs, and bone growth (23). Vitamin D [1406-16-2] is most important for maintaining proper calcium absorption from the small intestine. It also aids in mobilizing calcium from bones and in optimizing absorption of phosphoms from the small intestine (23). Supplementation of vitamins A and D at their minimum daily requirement is recommended because feedstuffs are highly variable in their content of these vitamins. 

Castor Oil. Castor oil [8001-79-4] (qv) is the fixed oil from the seeds of Picinus communis Linne. Pale yellowish or almost colorless, it is a transparent viscid Hquid with a faint, mild odor and a bland taste followed by a slightly acrid and usually nauseating taste. Its specific gravity is between 0.945 and 0.965. Castor oil is soluble in alcohol, and miscible with anhydrous alcohol, glacial acetic acid, chloroform, and diethyl ether. It consists chiefly of the glycerides of ricinoleic acid [141 -22-0], and isoricinoleic acid [73891-08-4], found in the small intestine. The seed contains a highly... 

Castor oil is a cathartic only after Hpolysis in the small intestine Hberating ricinoleic acid. Ricinoleic acid inhibits the absorption of water and electrolytes. It is commonly used for preparation of the large bowel for diagnostic procedures. 

Lactulose. 4-O-P -D-Galactopyranosyl-4-D-fmctofuranose [4618-18-2] (Chronolac) (12) may be made from lactose using the method described in Reference 9. It is a synthetic disaccharide that is not hydroly2ed by gastrointestinal enzymes in the small intestine, but is metabolized by colonic bacteria to short-chain organic acids. The increased osmotic pressure of these nonabsorbable organic acids results in an accumulation of fluid in the colon. Lactulose may not be tolerated by patients because of an extremely sweet taste. It frequently produces flatulence and intestinal cramps. 

Diarrhea is a common problem that is usually self-limiting and of short duration. Increased accumulations of small intestinal and colonic contents are known to be responsible for producing diarrhea. The former may be caused by increased intestinal secretion which may be enterotoxin-induced, eg, cholera and E. col] or hormone and dmg-induced, eg, caffeine, prostaglandins, and laxatives decreased intestinal absorption because of decreased mucosal surface area, mucosal disease, eg, tropical spme, or osmotic deficiency, eg, disaccharidase or lactase deficiency and rapid transit of contents. An increased accumulation of colonic content may be linked to increased colonic secretion owing to hydroxy fatty acid or bile acids, and exudation, eg, inflammatory bowel disease or amebiasis decreased colonic absorption caused by decreased surface area, mucosal disease, and osmotic factors and rapid transit, eg, irritable bowel syndrome. 

Small intestinal mucosV placenta, liver, skin, kidney, thymus, eosinophil, neutrophi... 

Acarbose is a nonabsorbable a-glucosidase inhibitor which blocks the digestion of starch, sucrose, and maltose. The digestion of complex carbohydrates is delayed and occurs throughout the small intestine rather than in the upper part of the jejunum. Absorption of glucose and other monosaccharides is not affected. Acarbose is adrninistered orally three times a day and chewed with the first mouthful of food. 

The largest use of endoscopic techniques is in the examination of the gastrointestinal tract. Upper intestinal endoscopy is the examination of the esophagus, stomach, and proximal duodenum. Colonoscopy is the examination of the colon, large intestine, and in some cases the distal parts of the small intestine. Cholangiopancreatography is the examination of the biUary tree and pancreas. 

Florfenicol concentrations in tissues and body fluids of male veal calves were studied after 11 mg/kg intramuscular doses adininistered at 12-h intervals (42). Concentrations of florfenicol in the lungs, heart, skeletal muscle, synovia, spleen, pancreas, large intestine, and small intestine were similar to the corresponding semm concentrations indicating excellent penetration of florfenicol into these tissues. Because the florfenicol concentration in these tissues decreased over time as did the corresponding semm concentrations, it was deemed that florfenicol equiUbrated rapidly between these tissues and the blood. Thus semm concentrations of florfenicol can be used as an indicator of dmg concentrations in these tissues. 

Metabolism. Absorption, distribution, metaboHsm, and excretion of thioglycolic acid have been reviewed (20). In summary,. -thioglycolic acid was absorbed significantly after appHcation to the skin of rabbits. After intravenous injection, the greatest counts of radioactivity were found in the kidneys, lungs, and spleen of monkey and in the small intestine and kidneys of rat. Most of the radioactivity was rapidly excreted in the urine in the form of inorganic sulfate and neutral sulfur. 

Absorption, Transport, and Excretion. The vitamin is absorbed through the mouth, the stomach, and predominantly through the distal portion of the small intestine, and hence, penetrates into the bloodstream. Ascorbic acid is widely distributed to the cells of the body and is mainly present in the white blood cells (leukocytes). The ascorbic acid concentration in these cells is about 150 times its concentration in the plasma (150,151). Dehydroascorbic acid is the main form in the red blood cells (erythrocytes). White blood cells are involved in the destmction of bacteria. 

Food vitamin B 2 appears to bind to a saUvary transport protein referred to as the R-protein, R-binder, or haptocorrin. In the stomach, R-protein and the intrinsic factor competitively bind the vitamin. Release from the R-protein occurs in the small intestine by the action of pancreatic proteases, leading to specific binding to the intrinsic factor. The resultant complex is transported to the ileum where it is bound to a cell surface receptor and enters the intestinal cell. The vitamin is then freed from the intrinsic factor and bound to transcobalamin II in the enterocyte. The resulting complex enters the portal circulation. 

Intestinal Fluke. The intestinal fluke, Fascio/opsis huski which can reach a length of 8 cm, Hves attached to the wall of the small intestine. 

Both the adult and the larval cysticerci (bladderworm) of Taenia solium (pork tapeworm) are able to Hve in humans the parasite is found sporadically in uncooked pork. In the stomach, the larva is digested out of the pork flesh it then grows and attaches to the wall of the small intestine. Maturity is reached in 5—12 weeks. The adult is 5 m long, and untreated adult worms may survive for 25 years. 

Hexamitosis is a disease of chickens, turkeys, quail, and pheasants in which there is an infectious catarrhal enteritis in the duodenum and small intestine. 

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