The small intestine is the principal site for absorption of nutrients and it is also where most orally-administered drugs enter the body. This part of the gut has two important attributes, an enormous surface area due to the intestinal villi, and an epithelium through which fluid readily filters in response to osmotic differences caused by the presence of food. It follows that drug access to the small intestinal mucosa is important and disturbed alimentary motility can reduce absorption, i.e. if gastric emptying is slowed by food, or intestinal transit is accelerated by gut infection. The colon is capable of absorbing drugs and many sustained-release formulations probably depend on absorption there.
Absorption of ionisable drugs from the buccal mucosa is influenced by the prevailing pH which is 6.2-7.2. Lipid-soluble drugs are rapidly effective by this route because blood flow through the mucosa is abundant and entry is directly into the systemic circulation, avoiding the possibility of first-pass (presystemic) inactivation in the liver (see below). The stomach does not play a major role in absorbing drugs, even those that are acidic and thus unionised and lipid-soluble at gastric pH, because its surface area is much smaller than that of the small intestine and gastric emptying is speedy (t\ 30 min).
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