Small intestine secretions drug absorption

Terao, T., Hisanaga, E., Sai, Y., Tamai, I., Tsuji, A., Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier,... 

SALSALATE (Saiicyisaiicyiic Acid) After absorption, the drug is partially hydrolyzed into two molecules of salicylic acid. Insoluble in gastric secretions, it is not absorbed until it reaches the small intestine. 

Antimotility drugs are opioid drugs. They increase small bowel smooth muscle tone and segmentation activity. They also reduce propulsive movements and decrease intestinal secretions while increasing absorption. They mediate these actions through p receptors. 

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 drug-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. 

The Small Intestine and Secretions Relevant to Drug Absorption... 

Preliminary pharmacokinetic behavior can be tested through a number of whole cell assays. Most commercially successful drugs are administered orally, meaning the drug must be able to enter the bloodstream by crossing membranes in the intestines. The most common membrane permeability assay is performed by monitoring the absorption and secretion of a compound by colon carcinoma cells (Caco-2). Diffusion across Caco-2 cell membranes is considered to be a valid model for molecular transport in the small intestines.16... 

Oral administration is the most common route of drug administration. Major physiologic processes in the GI system include secretion, digestion, and absorption. Secretion includes the transport of fluid, electrolytes, peptides, and proteins into the lumen of the alimentary canal. Enzymes in saliva and pancreatic secretions are involved in the digestion of carbohydrates and proteins. Other secretions such as mucus protect the linings of the lumen of the GI tract. Digestion is the breakdown of food constituents into smaller structures in preparation for absorption. Both drug and food constituents are mostly absorbed in the proximal area (duodenum) of the small intestinal. The process of absorption is the entry of constituents from the lumen of the gut into the body. Absorption may be considered as the net result of both lumen-to-blood and blood-to-lumen transport movements. 

Luminal and Membrane Metabolism of Peptides and Proteins. In meaningful studies on peptide and protein drug absorption in the small intestine, it is prerequisite to distinguish among cavital, membrane contact, and intracellular drug metabolism.Cavital metabolism takes place in the lumen of the small intestine by enzymes such as trypsin, chymotrypsin, carboxypepti-dase, and elastase, which are secreted by the pancreas. Membrane contact metabolism is carried out by aminopeptidases lo-calized on the brush border membrane. Intracellular metabolism occurs inside of the cells. The known intra-celluar enzymes are cytoplasmic peptidases, prolidase, dipeptidase, and tripeptidase.A more detailed dis-cussion of this topic is presented in section Intestinal Absorption Barriers, later. 

Cells throughout the gastrointestinal tract release somatostatin. Somatostatin inhibits acid secretion in the stomach and it promotes absorption of sodium, chloride and water in the small intestine and colon (Krejs 1986). The somatostatin analogs octreotide and lanreotide have been shown to decrease intestinal secretion in animal models (Botella et al 1993) and in humans with specific metabolic intestinal secretory disorders however, these drugs are not used widely in human medicine. In one study in horses, octreotide was shown to decrease gastric acidity (Sojka et al 1992) but its effects on intestinal or colonic secretion in horses have not been reported. 

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