In addition to the lipid-water partition coefficient of drugs, local blood flow, and intestinal surface area, other factors may affect absorption from the gastrointestinal tract.
The rate of gastric emptying markedly influences the rate at which drugs are absorbed, whether they are acids, bases, or neutral substances. In general, factors that accelerate gastric emptying time, thus permitting drugs to reach the large absorptive surface of the small intestine sooner, will increase drug absorption unless the drug is slow to dissolve. A list of physiological, pathological, and pharmacological factors that in fluence the rate of gastric emptying is provided in Table 3.1.
Increased gastrointestinal motility may facilitate drug absorption by thoroughly mixing intestinal contents and thereby bringing the drug into more intimate contact with the mucosal surface. However, the opposite may also occur in that an increase in motility may reduce contact time in the upper portion of the intestine where most of drug absorption occurs. Conversely, a decrease in gastrointestinal motility may promote absorption by increasing contact time. Thus, the effect depends on the drug and change in motility. Serious intestinal diseases, particularly those associated with intestinal sloughing, can be expected to alter drug absorption dramatically.
Absorption of most drugs from the gastrointestinal tract is reduced or delayed by the presence of food in the gut. Drugs such as the tetracyclines, which are highly ionized, can complex with Ca++ ions in membranes, food, or milk, leading to a reduction in their rate of absorption. For drugs that are ionized in the stomach and un-ionized in the intestine, overall absorption will be delayed by any factor that delays gastric emptying. Finally, increased splanchnic blood flow, as occurs during eating, will increase the rate of drug absorption.
The ability of solid drug forms to dissolve and the solubility of the individual drug in the highly acidic gastric juice must be considered. For example, although the anticoagulant dicumarol has a very high lipid-water partition coefficient, it precipitates at the low pH of gastric juice, and the rate of its absorption is
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