Stomach oral administration routes

The oral administration route is most common, especially for chronic diseases that require constant medication. Through this route, the drug has to go through the entire digestive tract where it is exposed to different physiological conditions such as pH and enzymatic activity of organs such as the stomach, small intestine, and colon [64]. 

Oral (PO = per os) By the mouth. Oral administration is the most common route employed for a variety of dosage forms tablets, capsules, liquids, suspensions. The major site of absorption is the small intestine. Alcohol is absorbed from the stomach. 

Autopsy tissues and other biologic specimens from people fatally poisoned with endrin (by the oral or an unspecified route) were analyzed (Tewari and Sharma 1978). The "fatal period" (presumed to be the time from onset of symptoms until death) for the subjects studied ranged from 1 to 6 hours. As is characteristic of oral administration, highest tissue concentrations were observed in the stomach (1.04-14.5 mg/100 g), intestine (1.31-66 mg/100 g), and liver (0.94-20 mg/100 g), followed by kidney, spleen, heart, and lung. Blood concentrations were low (0.43-0.85 mg/100 g) compared to tissue concentrations. 

These results are similar to those after oral administration and suggest that 1,2-dibromoethane is rapidly absorbed and distributed but retained to only a limited extent mainly in the kidneys, liver, and stomach, regardless of the route of exposure and the species tested. 

Insulin, a large polypeptide, is not suitable for oral administration. Even if the insulin molecule survived digestion by proteases in the stomach and small intestine, this compound is much too large to be absorbed through the gastrointestinal wall. Consequently, insulin is usually administered through subcutaneous injection. Insulin may also be administered by the intravenous route in emergency situations (e.g., diabetic coma). 

The large instability of A -tetrahydrocannabinol in acid solution (16,18), implies that the drug may be significantly degraded in the normal stomach. Again, this intimates that oral administration may not be an optimum route on which to establish dose-response correlations. Furthermore, the choice of a cannabinoid as an internal standard is very critical since it must not give any interference with the other related compounds, unless a HPLC purification step is included in the procedure. Cannabinol which, at times, has been taken as a possible metabolite (19-21) of A9-tetrahy-drocannabinol, may only be an artifact of the analytical procedure since disproportionation of 1 occurs readily. 

Regarding to the acute toxicity, MC-LR is highly toxic (LDjq 25-50 pg kg by i.p. route) the oral LDjq is 5000 pg Kg in mice. Yoshida (1997) has indicated that even by the oral route, micro-cystin-LR displays acute toxicity in rodents. There is no evidence of lydrolysis of microcystins by peptidases in the stomach, and it is apparent that a sigiuficant amount of microcystin-LR passes the intestinal barrier and is absorbed. The i.p. LD q of several of the conunon occurring microcystins (MC-LA,-YR,-YM) are similar to that of MC-LR but for MC-RR is tenfold higher however, because of differences in lipophilicity and polarity between the different microcystins, it cannot be presumed that the i.p LD q will predict toxicity after oral administration. 

For perhaps a last word, it is said that amygdahn or laetrile will release cyanide in the stomach by the action of the enzyme P glucosidase, also called emulsin (Smith, in Amdiu et al., 1991, p. 277). Not found in mammalian tissues, such enzymes occur in normal human intestinal flora, or gut flora. For this reason, amygdalin is about 40 times more toxic by mouth than by intravenous injection. Thus amygdalin or laetrile could be given safely by parenteral routes. (The term parenteral signifies routes other than oral administration.)... 

The oral route is undoubtedly the most widely investigated alternative administration route however, it presents major concerns in the delivery of macromolecular actives. The gastrointestinal route can promote degradation in the stomach due to the acidic gastric pH. The intestine has issues arising from the presence of proteolytic enzymes and insufficient permeation toward these actives, all of which result in limited bioavailability. Therefore, other routes of delivery have been investigated and the oral mucosal route presents a convenient alternative. 

However, the remaining problem was the administration route of the drug. Shortly before the Second World War, Inhoffen had prepared 17a-ethynyl-oestradiol, and had noticed that this derivative is surprisingly stable in the stomach. The initial objective of Inhoffen s synthesis was actually oestradiol-17-car-boxylic acid, which ought to have been produced by ethynylation and ozonoly-sis. Fortunately, the intermediate was also checked for its oral bioavailability. In fact, the carboxylic acid was only synthesised 50 years later and proved to be completely inactive. [24]... 

Oral administration of drugs is the most acceptable route of administration. However, the oral route for delivering protein and peptides continues to pose significant challenges. The main reasons for low oral bioavailability of proteins and peptides are presystemic enzymatic degradation and proteolysis in the stomach. However, several reports suggest that nutritional proteins are absorbed through intestinal mucosa and small amounts of peptides can be absorbed by specific transporters expressed on intestinal epithelium [2]. Over the past few years, extensive research has been carried out to delineate... 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

It might be expected that EN via tubes would have been used widely before the development of parenteral nutrition (PN) however, this was not actually the case. EN via tubes inserted down the mouth or nose into the stomach and also via rectal tubes was used occasionally in the decades before the development of PN in the 1960s.1 However, modern techniques for enteral access, both the placement of the tubes themselves and the materials for making pliable, comfortable tubes, had not yet been developed. Before the PN era, the formulas delivered by the tube route often were blenderized foods. The National Aeronautics and Space Administration effort in the United States in the 1960s led to the development of low-residue (monomeric) diets for astronauts. These diets were adapted for use in sick patients requiring EN. Nonvolitional feedings in patients who cannot meet nutritional requirements by oral intake thus include EN and PN these techniques are collectively known as specialized nutrition support (SNS). 

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