Absorption, of foreign compounds

Figure 3.4 Role of blood flow and ionization in the absorption of foreign compounds. Both blood flow and ionization create a gradient across the membrane.

There are a number of factors that affect the absorption of foreign compounds from the gut or their disposition one factor, which is of particular importance, is the aqueous solubility of the compound in the nonionized form. With very lipid-soluble compounds, water solubility may be so low that the compound is not well absorbed (Table 2), because it is not dispersed in the aqueous environment of the gastrointestinal tract. In relation to this, a factor of particular importance in absorption of chemicals from the gut is the presence of bile, which is produced in the liver and secreted into the small intestine. This contains detergent-like substances, which will facilitate the dispersal of lipid-soluble chemicals in the aqueous medium of the intestine. 

Apart from influencing the absorption of foreign compounds, the environment of the gastrointestinal tract may also affect the compound itself, making it more or less toxic. For example, gut bacteria may enzymically alter the compound, and the pH of the tract may affect its chemical structure. 

Absorption. Absorption of foreign compounds from various sites is dependent on the physiological and physical conditions at these sites. These, of course, may be subject to species variations. Absorption of compounds through the skin shows considerable species variation. Table 5.2 gives an example of this and shows the species differences in toxicity of an organophosphorus compound absorbed percutaneously. Human skin is generally less permeable to chemicals than that of rabbits, mice, and rats, although there is variation. For some compounds, rat skin has similar permeability to human skin and seems to be less permeable than that of the rabbit. 

Although the toxicological significance has yet to be studied, age-related differences in the absorption of foreign compounds are demonstrable. Neonatal and geriatric human subjects have low gastric acid secretion, and consequently the absorption of some foreign compounds may be altered. Thus in the neonate, penicillin absorption is enhanced, whereas paracetamol absorption is decreased. 

Intestinal motility may also be influenced by age, with various effects on the absorption of foreign compounds dependent upon the site of such absorption. The absence of gut flora in... 

Although there are several sites of first contact between a foreign compound and a biological system, the absorption phase (and also distribution and excretion) necessarily involves the passage across cell membranes whichever site is involved. Therefore, it is important first to consider membrane structure and transport in order to understand the absorption of toxic compounds. 

Many foreign substances are ingested orally, either in the diet or as drugs, and poisonous substances taken either accidentally or intentionally. Most suicidal poisonings involve oral intake of the toxic agent. Consequently, the gastrointestinal tract is a very important site and perhaps the major route of absorption for foreign compounds. 

The rates of movement of foreign compound into and out of the central compartment are characterized by rate constants kab and kei (Fig. 3.23). When a compound is administered intravenously, the absorption is effectively instantaneous and is not a factor. The situation after a single, intravenous dose, with distribution into one compartment, is the most simple to analyze kinetically, as only distribution and elimination are involved. With a rapidly distributed compound then, this may be simplified further to a consideration of just elimination. When the plasma (blood) concentration is plotted against time, the profile normally encountered is an exponential decline (Fig. 3.24). This is because the rate of removal is proportional to the concentration remaining it is a first-order process, and so a constant fraction of the compound is excreted at any given time. When the plasma concentration is plotted on a logio scale, the profile will be a straight line for this simple, one compartment model (Fig. 3.25). The equation for this line is... 

The importance of the physicochemical characteristics of compounds has already been alluded to in the previous two chapters. Thus, lipophilicity is a factor of major importance for the absorption, distribution, metabolism, and excretion of foreign compounds. Lipophilic compounds are more readily absorbed, metabolized, and distributed, but more poorly excreted, than hydrophilic compounds. 

In addition to its role in surfactant production, the type II cell also has a progenitor function, acting as the stem cell of the alveolar epithelium. The alveolar type I cells are highly susceptible to injury by oxygen and a variety of noxious substances. In such situations, type II cells can differentiate into type I cells and thus regenerate the gas-exchanging alveolar surface. Other functions of the type II cell are also believed to be the metabolism of foreign compounds (xenobiotic metabolism) and fluid and electrolyte absorption from the alveolar sacs into the interstitial matrix that surrounds the alveoli. 

Ayrton, A., 8c Morgan, P. (2001). Role of transport proteins in drug absorption, distribution and excretion. XenoUotica The Fate of Foreign Compounds in Biological Systems, 31, 469—497. 

Figure 3.8 Blood flow and resulting distribution of a foreign compound from the three major sites of absorption or routes of injection. Abbreviations, i.v., intravenous injection s.c., subcutaneous injection i.m., intramuscular injection i.p., intraperitoneal injection.

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