Enzyme activity oral mucosa

The oral mucosa, in common with other mucosa, shows enzymatic activity, in particular esterase and peptidase activity. Depending on the animal species and substrates used, buccal homogenates have shown enzyme activites between a few and several hundred percent of the activities of intestinal homogenates. 

In general, it can be said that enzyme levels are generally lower in the mouth than, for example, levels present in the gastrointestinal tract. Again, this lower metabolic activity makes the oral mucosa an attractive route for the delivery of enzymatically labile biopharmaceuticals. 

Several PAHs discussed in this profile have been shown to alter enzyme activity in the intestinal mucosa of animals following oral administration, which could conceivably lead to increased production of reactive intermediates and tissue injury. Given the selectivity of PAHs for rapidly proliferating tissues such as gastrointestinal mucosa and the results discussed above, exposure to PAHs (particularly oral) by humans could lead to adverse gastrointestinal effects. 

Advantages of the oral mucosal route of delivery include its capacity to bypass all the limitations associated with the oral route, ease of administration, relatively low content of enzymes, and adequate vascular drainage. As described in the following sections, most of the limitations of the oral mucosa epithelium arise from its stratified nature and its intercellular content characteristics. Nonetheless, due to its direct connection to systemic circulation, delivery systems could potentially be formulated to show either bolus-like or controlled release profiles for specific therapeutic needs. Polymers used in the development of such delivery systems play a major role in the release profile, permeation enhancement, and the localization of the active in the vicinity of the absorbing mucosa. Among the various uses of polymers in delivery systems, their mucoadhesive nature is the most prominent application in the oral mucosal route and is the main focus of this entry. After describing the physiological considerations in the oral cavity mucosa, this entry will review the literature pertinent to the use of polymers in delivery systems for the oral mucosal route. 

After oral administration, acetylsalicylic acid is rapidly and almost completely absorbed but in the intestinal mucosa it is partly deacetylated to salicylic acid, which also exhibits analgesic activity. The plasma half-life of acetylsalicylic acid is 15 min whereas that of salicylic acid, at low dosages of acetylsalicylic acid, is 2-3 h. Salicylic acid is eliminated more slowly when acetylsalicylic acid is administered at high dose rates because of saturation of the liver enzymes. The metabolites are mainly excreted via the kidney. 

Pancreatic enemies (B) from slaughtered animals are used to relieve excretory insufficiency of the pancreas ( disrupted digestion of fats steatorrhea, inter alia). Normally, secretion of pancreatic enzymes is activated by cholecystokinin ancreozymin, the en-terohormone that is released into blood from the duodenal mucosa upon contact with chyme. With oral administration of pancreatic enzymes, allowance must be made for their partial inactivation by gastric acid (the lipases, particularly). Therefore, they are administered in acid-resistant dosage forms. 

Estrogens are administered orally, parenterally by injection or as subcutaneous implants, transdermally and topically. After oral administration a considerable first pass effect, both in the intestinal mucosa and in the liver, takes place with large interindividual variability. Estrogens are hydroxylated and conjugated in the liver and excreted mainly in the bile. The conjugates can be hydrolyzed in the intestine to active compounds that are reabsorbed again. Their hepatic oxidative metabolism is increased by enzyme inducers and the enterohepatic circulation may be decreased by some antibiotics which disturb the intestinal bacterial flora. 

The in vivo metabolism of capecitabine (1) to the active tumor cytotoxic substance 5-fluorouracil (5) is now fairly well understood. When capecitabine is administered orally it is delivered to the small intestine, where it is not a substrate for thymidine phosphorylase in intestinal tissue, and so passes through the intestinal mucosa as an intact molecule and into the bloodstream. When 1 reaches the liver, the carbamate moiety is hydrolyzed through the action of carboxylesterase enzymes, liberating 5 -deoxy-5-fluorocytidine (5 -DFCR, 10). DFUR is partially stable in systemic circulation, but eventually diffuses into tumor cell tissue where it is transformed into 5 -deoxy-5-fluorouridine (5 -DFUR, 9) by cytidine deaminase, an enzyme present in high concentrations in various types of human cancers compared to adjacent healthy cells (although it is present in significantly lower levels in the liver). Within the tumor, 5-... 

Disposition in the Body. Rapidly absorbed from the small bowel after oral administration and widely distributed in the tissues less than 1% of a dose reaches the brain bioavailability about 33%. Extensively metabolised mainly by decarboxylation to dopamine, which is further metabolised, and also by methylation to 3-0-methyldopa which accumulates in the central nervous system most of a dose is decarboxylated by the gastric mucosa before entering the systemic circulation the decarboxylase activity is inhibited by carbidopa and benserazide. Dopamine is further metabolised to noradrenaline, 3-methoxytyramine, and to the two major excretory metabolites, 3,4-dihydroxyphenyl-acetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid, HVA). During prolonged therapy, the rate of levodopa metabolism appears to increase, possibly due to enzyme induction. About 70 to 80% of a dose is excreted in the urine in 24 hours. Of the material excreted in the urine, about 50% is DOPAC and HVA, 10% is dopamine, up to 30% is... 

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