Passive diffusion mechanisms

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... 

The following physicochemical properties are important for chemical diffusion. We have discussed several of these properties in previous sections of this chapter as they relate to the passive diffusion mechanism and its impacts on rate of toxicant transport across membranes. 

However, this is a rather simplistic view and it is important to realize that these considerations are only broad generalizations. Thus although a drag molecule may be predominantly absorbed via one particular route/mechanism, it is also likely that suboptimal transport will occur via other routes and mechanisms. In particular, drags that are absorbed via active mechanisms are often also absorbed, to a (much) lesser extent, via passive diffusion mechanisms. 

For drugs absorbed via passive diffusion mechanisms (paracellular or transcellular), increasing the area of the patch should increase the amount of drug absorbed. However, patch size must always be considered with respect to patient comfort and acceptability and must not be too large so that these factors are compromised. Thus the size of adhesive patches is generally in the range 2-5 cm2, with 10-15 cm2 being the upper limit. 

Bile salts are reabsorbed along the whole small intestine. The mechanism of absorption appears to vary depending upon the type of conjugate involved. Taurine conjugates are absorbed mainly in the lower ileum by both active and passive diffusion mechanisms. Whereas glycine conjugates— particularly those of the dihydroxy bile acids—are absorbed in the entire intestine by passive ionic diffusion, free bile acids are reabsorbed only in negligible amounts. 

The fat-soluble vitamins A, D, E and K pass through the intestinal mucosa mainly by the same passive diffusion mechanism as for fats.AMthin the cells they may combine with proteins and enter the general circulation as lipoproteins. 

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