Factors affecting disposition absorption

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. 

Other factors are that aleohol inereases the bioavailability of clomethiazole (probably by impairing first pass metabolism), and in the case of those with alcoholic cirrhosis, the systemic bioavailability may be increased tenfold because of venous shunting. However, one study in 6 healthy subjects reported that intravenous alcohol 0.8 mL/kg given acutely had no effect on the disposition or elimination of clomethiazole. It was proposed that alcohol given orally might affect the absorption or rate of uptake of clomethiazole. ... 

Table 6.1 Factors That May Affect Pulmonary Drug Absorption and Disposition (Modified from Tronde [139]). ...

Biological factors. The species of animal is a very important factor especially affecting metabolism but also influencing the other phases of disposition. The pH of the gastrointestinal tract, the nature of the skin, and breathing rate all may affect absorption. Plasma proteins and fat can affect distribution. Biliary excretion is affected by species in relation to the molecular weight threshold. 

As important as this pH effect is, it can be subordinated by other factors. For example, as indicated earlier, the absorptive area that a drug is exposed to can be a predominating factor. In this context, even though the acidic environment of the stomach favors the absorption of weak acids (e.g., acetylsalicylic acid), aspirin is still absorbed to a greater extent, in totality, in the small intestine. A partial list of the pH of several body compartments is shown in Table 2.4. The fact that there are some variations suggests that the disposition of some drugs may be differentially affected. 

Within human beings many factors can affect the processes of absorption of chemicals, their distribution throughout the body, metabolism, and excretion. Factors such as the age of the person, their state of health, their genetic make-up, their diet, and what drugs they are taking can all influence the disposition of a drug. 

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