Sites of Absorption

The rate or extent of drug absorption from the gastrointestinal tract can be influenced in a number of ways. Examples of these various influences follow. 

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Table 3. Primary Sites of Absorption and Excretion of Mineral Nutrients...

Swallowing. If it is sufficiently irritant or caustic, a swallowed material may cause local effects on the mouth, pharynx, esophagus, and stomach. Additionally, carcinogenic materials may induce tumor formation in the alimentary tract. Also, the gastrointestinal tract is an important route by which toxic materials are absorbed. The sites of absorption and factors regulating absorption have been reviewed (42,43). 

Materials may be absorbed by a variety of mechanisms. Depending on the nature of the material and the site of absorption, there may be passive diffusion, filtration processes, faciHtated diffusion, active transport and the formation of microvesicles for the cell membrane (pinocytosis) (61). EoUowing absorption, materials are transported in the circulation either free or bound to constituents such as plasma proteins or blood cells. The degree of binding of the absorbed material may influence the availabiHty of the material to tissue, or limit its elimination from the body (excretion). After passing from plasma to tissues, materials may have a variety of effects and fates, including no effect on the tissue, production of injury, biochemical conversion (metaboli2ed or biotransformed), or excretion (eg, from liver and kidney). 

The exact site of anthocyanin absorption is not fully known recently it was suggested that the stomach is one of the preferential sites for the process in humans. Interestingly, anthocyanin glycosides are efhciently absorbed in rats (up to 25%) from both stomach " and small intestine, suggesting that anthocyanins have more than one site of absorption along the intestinal tract. 

Pq, characterizes the membrane transport of the uncharged species. The concentration of the uncharged species, Cq, depends on the dose, the solubility, the pKa of a molecule and the pH at the site of absorption, often according to the Henderson-Hasselbalch equation [8]. 

The fact that the GIT is so well perfused by the bloodstream permits efficient delivery of absorbed materials to the body. As a result of this rapid blood perfusion, the blood at the site of absorption represents a virtual sink for absorbed material. Under normal conditions, then, there is never a buildup in drug concentration in the blood at the site of absorption. Therefore, the concentration gradient will favor further unidirectional transfer of drug from the gut to the blood. Usually, then, blood flow is not an important consideration in drug absorption. Generally, the properties of the dosage form (especially dissolution rate) or the compound s inherent absorbability will be the limiting factors in absorption. 

V. MOVING THE DRUG AWAY FROM THE SITE OF ABSORPTION... 

The receiver compartment in the GIT has a strong sink condition, effected by serum proteins. In contrast, the BBB does not have a strong sink condition. In the GIT, lipophilic molecules are swept away from the site of absorption in... 

Delivery of either a small or large dose of the drug at the same rate Delivery of drug at the intended site of absorption irrespective of the region of the gastrointestinal tract where that process occurs... 

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. 

The important stages in delivering a drug to its desired target after an oral dose can be summarized as shown in Fig. 6.2. Initially the formulation has to be swallowed and survive the transition to the site of absorption - the gastrointestinal tract (GIT). The time required for this to happen will depend on the stomach emptying time, which in turn will be a function of the fed/fasted state of the subject or animal that is being studied (see for example Ref. [7]). This kind of information can only be obtained from in vivo studies. 

Chandler, P. T. and Cragle, R. G. (1962). Gastrointestinal sites of absorption and endogenous secretion of calcium and phosphorus in dairy calves, Proc. Soc. Exp. Biol. Med. Ill, 431. 

Another approach to characterise the site of absorption in the lipid bilayer is to analyse the dielectric properties of this site. The permittivity e in the hydro-phobic core of the membrane is very small (s of approximately 2 to 3), and rises outwards until it reaches the value in the aqueous phase (e = 78) [6], s is about 30 at the location of the carboxy groups of the fatty acid chain [150], Other measurements averaged to e of 30 to 33 at the interface between polar head groups and the hydrocarbon core [176]. The e of the absorption site of... 

The process by which a xenobiotic and its metabolites are transferred from the site of absorption to the blood circulation. 

When a drug has dissolved in the GI fluids and is present in solution at the site of absorption it has to pass a biological barrier, that is, the enterocytes lining the gut wall, in order to be absorbed into the body. The absorptive flux (J) can be described as a function of the permeability of the intestinal mucosa to the drug (Peff), the surface area available for absorption (SA), and the concentration gradient (AC) across the mucosa (e.g., [6], Eq. 2)... 

Absorption of phenol occurs fairly rapidly via the inhalation (Hughes and Hall 1995 Ohtsuji and Ikeda 1972 Piotrowski 1971), oral (Capel et al. 1972 Edwards et al. 1986 French et al. 1974 Hughes and Hall 1995 Kao et al. 1979 Kenyon et al. 1995), and dermal (Baranowska-Dutkiewicz 1981 Hughes and Hall 1995 Piotrowski 1971) routes. Because it is an irritant, tissue damage, inflammation, or other irritation effects may occur at the sites of absorption. Because of its high pKa, ionization will not occur within the acid environment of the gut. The action of gut microflora on phenol breakdown is not expected to be significant. 

Type of solution (aqueous vs. lipid) Rate of dissolution of solid drugs Concentrations of a drug present Blood flow to the site of absorption Surface area of absorption... 

The importance of tobacco includes both those constituents in smoke that may interact with nicotine directly, as well as those that indirectly influence a smoker s perception and behaviors. For example, some tobacco smoke constituents may alter the site of absorption of nicotine, such as bronchodilators (e.g., cocoa, licorice), which allow deeper inhalation and subsequent deposition of constituents in more highly permeable areas of the respiratory tract. Likewise, product changes to alter or control particle size, or to provide particulate carriers for vapor-phase smoke constituents, also could facilitate changes at the site of absorption (Ingebrethsen 1993). This would also include the use of acids or bases to alter the form of nicotine and basicity of smoke. Again, a wide range of relevant findings is indicated by internal documents (Ferris Wayne et al. 2006 Keithly et al. 2005 Pankow 2001). 

Noninvasive drug delivery may require the administration of the drug delivery system (DDS) at an epithelium as a suitable site of absorption of the active compormd. Such regions are usually called mucosae. In the human body several mucosal sites can be identified, the one mostly used for administration and absorption of therapeutics being the gastrointestinal route. In order to increase the residence time at these absorption sites, a so-called mucoadhesive delivery system has to be used. Generally, these systems consist of one or more types of hydrogels. 

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