Mechanism of absorption

Mucosal site Drug Proprietary name Dosage form 

Experiments with some analgesics showed that the highly lipid-soluble etorphine was absorbed several times more rapidly from the buccal cavity than the less lipid-soluble morphine. Impressive absorption has been 

It has been claimed that an oil/water partition coefficient in the range 40-2000 (log P of 

Rgure 9.15 Relationship between the log P of solute and the percentage absorption through the buccal mucosa of human subjects for bases (O) and acids ( ) 

Plotted from data from E. Lien etal., Drug lr)tell. Clin. Pharm., 5, 38 (1971). 

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Absorption processes are categorized based on the mechanism of absorption, as either chemical or physical. In addition, a number of hybrid absorption processes featuring both chemical and physical solvents have been developed. 

Based on the rapid appearance of clinical signs and cholinesterase inhibition, methyl parathion appears to be readily absorbed by humans and animals following inhalation, oral, and dermal exposure. Following oral administration of methyl parathion to animals, the extent of absorption was at least 77-80% (Braeckman et al. 1983 Hollingworth et al. 1967). No studies were located regarding the extent of absorption following inhalation and dermal exposure, or the mechanism of absorption. 

Anthocyanins are poorly absorbed from the gastrointestinal tract and the mechanisms involved remain unclear. These compounds are usually recovered in very small amounts in human serum after oral ingestion (less than 1% of the dose) or in the IN fraction after in vitro digestion (about 5%). ° Unlike other polyphenols, anthocyanins constitute an exception because intact glycosides are recovered in the body (without deglycosylation prior to absorption). - This may be explained by either the instability of the free aglycone form or by a specific mechanism of absorption for anthocyanins. 

Peres, J. (1999). Mechanisms of absorption of caseinophosphopeptide bound iron. /. Nutr. Biochem. 10, 215-222. 

The site and mechanism of absorption of ingested americium are not known. Based on studies of plutonium, it is likely that americium absorption occurs, at least to some extent, in the small intestine. Studies of the absorption of plutonium in preparations of in situ isolated segments of small intestine of immature miniature swine indicate that absorption of actinides can occur along the entire small intestine, with the highest rates of absorption occurring in the duodenum (Sullivan and Gorham 1982). 

Absorption. No studies were located regarding the mechanism of absorption in humans or animals after inhalation, oral, or dermal exposure to diisopropyl methylphosphonate. Both facilitated transport and diffusion through the lipophilic portions of the membrane could be involved in absorption processes. No data were found regarding lipid solubility or partition coefficients. 

A thorough discussion of the mechanisms of absorption is provided in Chapter 4. Water-soluble vitamins (B2, B12, and C) and other nutrients (e.g., monosaccharides, amino acids) are absorbed by specialized mechanisms. With the exception of a number of antimetabolites used in cancer chemotherapy, L-dopa, and certain antibiotics (e.g., aminopenicillins, aminoceph-alosporins), virtually all drugs are absorbed in humans by a passive diffusion mechanism. Passive diffusion indicates that the transfer of a compound from an aqueous phase through a membrane may be described by physicochemical laws and by the properties of the membrane. The membrane itself is passive in that it does not partake in the transfer process but acts as a simple barrier to diffusion. The driving force for diffusion across the membrane is the concentration gradient (more correctly, the activity gradient) of the compound across that membrane. This mechanism of... 

Since many essential nutrients (e.g., monosaccharides, amino acids, and vitamins) are water-soluble, they have low oil/water partition coefficients, which would suggest poor absorption from the GIT. However, to ensure adequate uptake of these materials from food, the intestine has developed specialized absorption mechanisms that depend on membrane participation and require the compound to have a specific chemical structure. Since these processes are discussed in Chapter 4, we will not dwell on them here. This carrier transport mechanism is illustrated in Fig. 9C. Absorption by a specialized carrier mechanism (from the rat intestine) has been shown to exist for several agents used in cancer chemotherapy (5-fluorouracil and 5-bromouracil) [37,38], which may be considered false nutrients in that their chemical structures are very similar to essential nutrients for which the intestine has a specialized transport mechanism. It would be instructive to examine some studies concerned with riboflavin and ascorbic acid absorption in humans, as these illustrate how one may treat urine data to explore the mechanism of absorption. If a compound is... 

In Sec. VII we dealt with methods of determining the rate (and mechanism) of absorption. In this section we will deal with methods of determining the extent of absorption. In every example, the calculation will involve a comparison between two studies carried out in the same group of volunteers on different occasions. Usually it will be necessary to assume that the volunteers behaved identically on both occasions, especially with regard to their pharmacokinetic parameters. 

LS Schanker. On the mechanism of absorption from the gastrointestinal tract. J Med Pharm Chem 2 343, 1960. 

Carotenoid absorption and metabolism have been comprehensively reviewed (Erdman et al., 1993 Parker, 1996 van Vliet, 1996 Furr and Clark, 1997 Yeum and Russell, 2002) and this chapter will focus only on recent advances in these areas. A particular emphasis will be placed on studies that used in vitro and cell culture models as tools to understand better the mechanisms of absorption on the molecular level. 

LeCluyse. In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoylcamitine.,... 

Muranishi, S., Yamamoto, A., Mechanisms of absorption enhancement through gastrointestinal epithelium, in Drug Absorption Enhancement, de Boer, A. G. (ed.), Harwood Academic Publishers, 1994, 67-100. 

Hochman, J., Artursson, P., Mechanisms of absorption enhancement and tight junction regulation, J. Controlled Release 1994, 29, 253-267. 

D. E. Leahy, J. Lynch, D. C. Taylor. Mechanisms of absorption of small molecules. In eds. L. F. Prescott and W. S. Nimmo, Novel Drug Delivery and its Therapeutic Application. Wiley, New York 1989, 33-44. 

Neither the mechanism of absorption nor the mechanism of distribution for hexachloroethane has been established. There are indications that free radical reactions may be responsible for some of the toxic effects of hexachloroethane in the liver (Town and Leibman 1984), but the data are not conclusive. When additional data on absorption, distribution and mechanism are available, compound-specific studies on methods for mitigation of toxic effects can be designed. 

Methods for Reducing Toxic Effects. No information was located on mitigating the specific effects of u-hexane intoxication. Since the mechanism of absorption is passive diffusion, removal from exposure stops absorption. Distribution is via partitioning based on physicochemical properties. 

Mechanisms of Absorption. Ingestion is generally referred to as oral or per oral (PO) exposure and includes direct intragastric exposure in experimental toxicology. The regions for possible agent action and absorption from PO absorption should, however, be considered separately. 

Perhaps the most important toxicological role played by the GI tract is its influence over the absorption of chemicals that enter it. That absorption rates vary widely among chemicals has been explained in Chapter 2, but how the GI tract and its contents contribute to this phenomenon was not explained. Mechanisms of absorption are many and varied, and are influenced by the type and quantity of food present at the time of chemical ingestion, the pH (degree of acidity) of various portions of the GI tract, and even the nature and activity of the microorganisms that normally live in the intestines. In fact, metabolism of certain chemicals brought about by these microorganisms can play a crucial role, not only in their absorption, but also in the nature of the systemic toxicity they ultimately produce. 

Does the drug share a common mechanism of absorption or disposition with another likely... 

For demonstration of suitability of a method, model drugs should represent a range of low (e.g., < 50%), moderate (e.g., 50-89%), and high >90%) absorption. Sponsors may select compounds from the list of drugs and/or chemicals provided in Attachment A or they may choose to select other drugs for which there is information available on mechanism of absorption and reliable estimates of the extent of drug absorption in humans. 

Mechanism of Absorption and Emission of Radiation of Photochemical Interest... 

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