THE MECHANISM OF ABSORPTION

The preceding analysis of the process of absorption is based on the two-film theory of Whitman 11. It is supposed that the two films have negligible capacity, but offer all the resistance to mass transfer. Any turbulence disappears at the interface or free surface, and the flow is thus considered to be laminar and parallel to the surface. 

An alternative theory described in detail in Volume 1, Chapter 10, has been put forward by Higbie 2 , and later extended by Danckwerts and Danckwerts and Kennedy14 in which the liquid surface is considered to be composed of a large number of small elements each of which is exposed to the gas phase for an interval of time, after which they are replaced by fresh elements arising from the bulk of the liquid. 

All three of these proposals give the mass transfer rate N A directly proportional to the concentration difference (CAi — CAL) so that they do not directly enable a decision to be made between the theories. However, in the Higbie-Danckwerts theory N A a s/Dj whereas NA x DL in the two-film theory. Danckwerts applied this theory to the problem of absorption coupled with chemical reaction but, although in this case the three proposals give somewhat different results, it has not been possible to distinguish between them. 

Absorption experiments in columns packed with spheres, 37.8 mm diameter, were also carried out by Davidson el al. 6 who absorbed pure carbon dioxide into water. When a small amount of surface active agent was present in the water no appreciable mixing was 

In an attempt to test the surface renewal theory of gas absorption, Danckwerts and Kennedy measured the transient rate of absorption of carbon dioxide into various solutions by means of a rotating drum which carried a film of liquid through the gas. Results so obtained were compared with those for absorption in a packed column and it was shown that exposure times of at least one second were required to give a strict comparison this was longer than could be obtained with the rotating drum. Roberts and Danckwerts therefore used a wetted-wall column to extend the times of contact up to 1.3 s. The column was carefully designed to eliminate entry and exit effects and the formation of ripples. The experimental results and conclusions are reported by Danckwerts, Kennedy, and Roberts110 who showed that they could be used, on the basis of the penetration theory model, to predict the performance of a packed column to within about 10 per cent. 

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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. 

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... 

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.,... 

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. 

Absorption of cholesterol in the small intestine contributes to maintaining whole-body cholesterol homeostasis, yet the mechanisms of absorption have not been completely defined. For many years it was believed that cholesterol, a normal component of cell membranes, simply diffused through the brush border membrane of enterocytes (Grundy, 1983 Westergaard and Dietschy, 1974). However, the discovery of specific transporters, receptors,... 

Methods for Reducing Toxic Effects. The mechanism of absorption and distribution of aluminum... 

White Phosphorus. There is limited information on the mechanisms of absorption of white phosphorus for any of the routes of exposure. Information on reducing peak absorption following acute oral exposure (Diaz-Rivera 1950), after white phosphorus-induced dermal bums (Rabinowitch 1943 Goldblatt and Oakeshott 1943 Jelenko 1974 Eldad and Simon 1991), and after acute eye exposure (Scherling and Blondis 1945) is available. No information on reducing absorption following inhalation exposure was located. 

The mechanism of absorption after SC or IM administration is thought to occur via the lymphatic system. The mAbs enter the lymphatic system by convective flow of interstitial fluid into the porous lymphatic vessels. The molecular mass cut-off of these pores is >100-fold the molecular mass of mAbs. From the lymphatic vessels, the mAbs are transported unidirectionally into the venous system. As the flow rate of the lymphatic system is relatively low, mAbs are absorbed over a long time period after administration. The resulting time of maximum concentration (tmax) is much later (typically 1-8 days), and the systemically available fraction (F) is equal or lower (typically 0.5-1.0) compared to the IV administration of mAbs. For example, SC injection of 40 mg adalimumab results in a tmax of approximately 5 days, and F is approximately 64%. 

Methods for Reducing Toxic Effects. There are no established methods for reducing absorption of DEHP or metabolites because the mechanism of absorption is not known. There have been no studies of compound-specific techniques for reducing DEHP body burden. External contact with DEHP can be treated by thoroughly washing the affected area. Activated carbon, possibly combined with a cathartic, will diminish absorption of ingested DEHP from the gastrointestinal tract (HSDB 2000). 

Hochman JH, Fix JA, LeCluyse EL (1994) In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoylcarnitine. J Pharmacol Exp Ther 269 813-822 Hoffman A, Qadri B (2008) Eligen insulin-a system for the oral delivery of insulin for diabetes. IDrugs 11 433 41... 

The mechanisms of absorption promotion proposed for the different compounds are numerous and it is likely that more than one mechanism is involved (see Section 8.6.1). 

The route of administration is an important factor in determining the rate and extent of absorption. For example, absorption after an oral dose can be relatively slow and erratic, whilst absorption from the lungs is usually fast because of the good blood supply. Most drugs are administered orally, and an understanding of the mechanism of absorption by this route is by far the most important for the toxicologist. 

Anthocyanins can be absorbed intact as glycosides (Figure 1.1). The mechanism of absorption is not known however, PassamontP found that anthocyanins can serve as ligands for bilitranslocase, an organic anion membrane carrier found in the epithelial cells of the gastric mucosa, and suggested that bilitranslocase could play a role in the bioavailability of anthocyanins. Table 1.3 presents a summary of the research that has demonstrated absorption of intact anthocyanins in the rat, pig or human. At least 13 different anthocyanins from 7 different food sources have been observed to be absorbed intact and to be present in plasma or urine (Table 1.3). In... 

The mechanism of absorption must always be evaluated when a sustained-release dosage form is considered. A drug that is passively absorbed throughout the GI tracts is an ideal candidate for sustained release. Drugs such as riboflavin, folic acid, aminopenicillins, amino-p-lactams and nucleoside analogs, which have windows of absorption due to site-specific and/or active transport processes, may have incomplete bioavailability when formulated in oral, sustained-release dosage forms. 

Problems of current interest to which we draw attention in this review are (1) the nature of adsorbed hydrogen, (2) the possibility of weak adsorption in excess of a monolayer and its influence on surface area determinations, (3) the adsorption/ absorption transition and the mechanism of absorption, and (4) the selectivity of H for special sites in alloys and the structural modifications in alloys caused by H. Finally, we shall comment briefly on the extent to which existing theoretical models can account for some of these features. 

The mechanism of absorption for metallic mercury vapors is rapid diffusion across alveolar membranes (Berlin et al. 1969 Clarkson 1989). Mercury distribution in the brains of mercury-sensitive SJL/N mice exposed for 10 weeks (5 days per week) to relatively high concentrations (0.5-1.0 mg/m3) of mercury vapor was found to be affected by the magnitude of exposure (Warfvinge 1995). In animals exposed to 0.5 mg/m3 for 19 hours a day or 1 mg/m3 for 3 hours a day, mercury was found in almost the entire brain, whereas in those exposed to 0.3 mg/m3 for 6 hours a day, mercury was primarily found in the neocortical layer V, the white matter, the thalamus, and the brain stem. In mice exposed to 1 mg/m3 for just... 

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