Drug absorption stomach secretions

The GI tract is the site of absorption for most nutrients. Thus, the GI tract has evolved to facilitate absorption of substances. The peristaltic action of the stomach, secretion of enzymes and hydrochloric acid, the villi and microvilli of the intestine, as well as the rich blood supply and lymphatics in this region, all facilitate absorption. Enteral absorption is generally by far the most effective drug delivery route and, whenever possible, drugs are administered in this way. 

Proton pump inhibitors (PPIs), eg, omeprazole, lansoprazole Irreversible blockade of H +, K+-ATPase pump in active parietal cells of stomach Long-lasting reduction of stimulated and nocturnal acid secretion Peptic ulcer, gastroesophageal reflux disease, erosive gastritis Half-lives much shorter than duration of action low toxicity reduction of stomach acid may reduce absorption of some drugs and increase that of others... 

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. 

D. Pancreatic Enzyme Replacements Steatorrhea, a condition of decreased fat absorption coupled with an increase in stool fat excretion, results from inadequate pancreatic secretion of lipase. The abnormality of fat absorption can be significantly relieved by oral administration of pancreatic lipase (pancrelipase) obtained from pigs. Pancreatic lipase is inactivated at a pH below 4.0 thus, up to 90% of an administered dose will be destroyed in the stomach, unless the pH is raised with antacids or drugs that reduce acid secretion. 

It is absorbed almost 100% after oral administration however, the food present in the stomach may delay its absorption considerably. It gets widely distributed in the body and even into the CSF. In plasma almost 98% is protein-bound. The volume of distribution (v/ ) stands at 0.9 mL.g Biotransformation in the liver helps in the elimination of almost 85% of the drug . An active and primary metabolite, deacetylrifampin, gets secreted right into the bile where it is effective therapeutically. 

As I have already shown, a few years later Bernard Brodie s students at the National Institutes of Health formalized Travell s results by developing their par-tition hypothesis to explain secretion of drugs by the stomach (Fig. 8-7, pp. 296-298). The hypothesis explained the secretion of basic drugs into acid solution, and they turned it around to explain the absorption of acid drugs from acid but not alkaline solutions. Salicylic acid pKa = 3.0) in 0.1 N HCl was absorbed by a rat s stomach to the extent of 61% in an hour. Likewise, acetanilide pKa = 0.3) was absorbed from an acid solution, but barbital and quinine, each having a high pKa, were not absorbed from a similar solution. 

Fig. 6 This schematic is an illustration of the GIT advanced compartmental transit model (stomach, seven small intestine compartments, colon, and nine enterocytes). The administered drug, after dissolution, becomes available for passive absorption and efflux secretion. The rate of drug transfer into and out of enterocyte compartments for each GIT lumen compartment is calculated by using the concentration gradient across the apical and basolatmal membranes. This figure is published with permission (Agoram et al. 2001)...

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