Oral Cavity and Sublingual Absorption
In contrast to absorption from the stomach and intestine, drugs absorbed from the oral cavity enter the general circulation directly. Although the surface area of the oral cavity is small, absorption can be rapid if the drug has a high lipid–water partition coefficient and therefore can readily diffuse through lipid membranes.
Since the diffusion process is very rapid for un-ionized drugs, pKa will be a major determinant of the lipid– water partition coefficient for a particular therapeutic agent. For instance, the weak base nicotine (pKa 8.5) reaches peak blood levels four times faster when absorbed from the mouth (pH 6), where 40 to 50% of the drug is in the un-ionized form, than from the gastrointestinal tract (pH 1–5), where the drug exists mainly in its ionized (protonated) form.
Absorption from the Stomach
Although the primary function of the stomach is not absorption, its rich blood supply and the contact of its contents with the epithelial lining of the gastric mucosa provide a potential site for drug absorption.
However, since stomach emptying time can be altered by many variables (e.g., volume of ingested material, type and viscosity of the ingested meal, body position, psychological state), the extent of gastric absorption will vary from patient to patient as well as at different times within a single individual.
Absorption from the Small Intestine
The epithelial lining of the small intestine is composed of a single layer of cells called enterocytes. It consists of many villi and microvilli and has a complex supply of blood and lymphatic vessels into which digested food and drugs are absorbed. The small intestine, with its large surface area and high blood perfusion rate, has a greater capacity for absorption than does the stomach. Most drug absorption occurs in the proximal jejunum (first 1–2 m in humans).
Although transfer of drugs across the intestinal wall can occur by facilitated transport, active transport, endocytosis, and filtration, the predominant process for most drugs is diffusion. Thus, the pKa of the drug and the pH of the intestinal fluid (pH 5) will strongly influence the rate of drug absorption. While weak acids like phenobarbital (pKa 7.4) can be absorbed from the stomach, they are more readily absorbed from the small intestine because of the latter’s extensive surface area.
Absorption from the Large Intestine
The large intestine has a considerably smaller absorptive surface area than the small intestine, but it may still serve as a site of drug absorption, especially for compounds that have not been completely absorbed from the small intestine. However, little absorption occurs from this site, since the relatively solid nature of the intestinal contents impedes diffusion of the drug from the contents to the mucosa.
The most distal portion of the large intestine, the rectum, can be used directly as a site of drug administration. This route is especially useful where the drug may cause gastric irritation, after gastrointestinal surgery, during protracted vomiting, and in uncooperative patients (e.g., children) or unconscious ones. Dosage forms include solutions and suppositories. The processes involved in rectal absorption are similar to those described for other sites.
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