Absorption sites

Fresh charcoal is a strong absorbent for gases, and this is an exothermic process. The heat generated can be enough to cause spontaneous ignition in some cases. Hence it is customaiy to age charcoal by exposure to air and thus cover the absorption sites with a layer of nitrogen gas. Larger molecules will desorb and replace smaller molecules, so the charcoal will still be effective as a decolorant or deodorizer. 

This model is representative for the conditions described in the previous section, except for the mode of administration which can be oral, rectal or parenteral by means of injection into muscle, fat, under the skin, etc. (Fig. 39.7). In addition to the central plasma compartment, the model involves an absorption compartment to which the drug is rapidly delivered. This may be to the gut in the case of tablets, syrups and suppositories or into adipose, muscle or skin tissues in the case of injections. The transport from the absorption site to the central compartment is assumed to be one-way and governed by the transfer constant (Fig. 39.7a). The linear differential model for this problem can be defined in the following way ... 

GIT, is considered to be lost from the absorption site, as is metabolic clearance and sequestration in various cell types and membranes (72,14). It is clear from Scheme I that the relative rates of the various processes will define the bioavailable fraction of the dose and understanding those factors which control pulmonary absorption kinetics is obviously the key to enhancing bioavailability via the lung. In a recent book (75) the molecular dependence of lung binding and metabolism was considered alongside the parallel processes of absorption, clearance and dissolution in the lung (14). Some key features of this work will be repeated as it relates to the systemic delivery of polypeptides. 

Physicochemical properties of the drug product Control and maintenance of the location of the drug product at the absorption site(s)... 

The analysis of absorption data in humans has moved away from the more traditional modeling and data fitting techniques [35]. Absorption processes are now more often characterized by a mean absorption (or input) time (i.e., the average amount of time that the drug molecules spend at the absorption site) or by a process called deconvolution. The former analysis results in a single value (similar to absorption half-life) and the latter results in a profile of the absorption process as a function of time (e.g., absorption rate or cumulative amount absorbed vs. time). These approaches offer additional ways of interpreting the absorption process. 

Once a drug is in solution at the absorption site, it must move through the GIT membrane and then into the general circulation. In Chapter 2 Fick s law was used to describe this transport ... 

Drugs that affect tissue properties, particularly blood flow at the absorption site, may be used to control the rate of absorption. Reduced drug absorption may be achieved physiologically with an IM preparation by incorporating epinephrine, which causes a local constriction of blood vessels at the site of injection. Increased muscular activity may enhance drug absorption because of increased drug flow. 

Dose response Absorption sites/rates Bioavailabilities (at receptor)... 

Lewis Bases. A variety of other ligands have been studied, but with only a few of the transition metals. There is still a lot of room for scoping work in this direction. Other reactant systems reported are ammoni a(2e), methanol (3h), and hydrogen sulfide(3b) with iron, and benzene with tungsten (Tf) and plati num(3a). In a qualitative sense all of these reactions appear to occur at, or near gas kinetic rates without distinct size selectivity. The ammonia chemisorbs on each collision with no size selective behavior. These complexes have lower ionization potential indicative of the donor type ligands. Saturation studies have indicated a variety of absorption sites on a single size cluster(51). 

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... 

Surfactants may increase the solubility of the drug via micelle formation, but the amounts of material required to increase solubility significantly are such that at least orally the laxative effects are likely to be unacceptable. The competition between the surfactant micelles and the absorption sites is also likely to reduce any useftd effect and make any prediction of net overall effect difficult. However, if a surfactant has any effect at all, it is likely to be in the realm of agents that help disperse suspensions of insoluble materials and make them available for solution. Natural surfactants, in particular bile salts, may enhance absorption of poorly soluble materials. 

Hydrodynamics in the upper GI tract contribute to in vivo dissolution. Our ability to forecast dissolution of poorly soluble drugs in vitro depends on our knowledge of and ability to control hydrodynamics as well as other factors influencing dissolution. Provided suitable conditions (apparatus, hydrodynamics, media) are chosen for the dissolution test, it seems possible to predict dissolution limitations to the oral absorption of drugs and to reflect variations in hydrodynamic conditions in the upper GI tract. The fluid volume available for dissolution in the gut lumen, the contact time of the dissolved compound with the absorptive sites, and particle size have been identified as the main hydrodynamic determinants for the absorption of poorly soluble drugs in vivo. The influence of these factors is usually more pronounced than that of the motility pattern or the GI flow rates per se. 

Rouge N, Buri P, Doelker E (1996) Drug absorption sites in the gastrointestinal tract and dosage forms for site-specific delivery. Int J Pharm 136 117-139... 

Matsuda K, Yuasa H, Watanabe J (1998) Fractional absorption of L-carnitine after oral administration in rats Evaluation of absorption site and dose dependency. Biol Pharm Bull 21 752-755... 

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