Gastrointestinal membrane

As described in Chapter 2, the extent of oral drug availability (Eoral) may be described as the product of absorption availability (Fabs), the extent of availability through the gastrointestinal membranes (FG), and the availability through the liver (F/f) ... 

With the weak acid, however, it can be appreciated that although most is in the ionized form in the small intestine, ionization in the plasma facilitates removal of the transported form, maintaining the concentration gradient across the gastrointestinal membrane (Fig. 3.15). Consequently, weak acids are generally fairly well absorbed from the small intestine. 

The phosphate ion readily passes across the gastrointestinal membrane. The rate of absorption of phosphate at various intestinal sites in rats has been observed to be most rapid in the duodenum, followed in decreasing order by the jejunum, ileum, colon, and stomach. When transit time is considered, most of the phosphorus is absorbed by the ileum. 

The oral bioavailability of a drug (F ) may be regarded as the product of the fraction of the drug dose absorbed into and through the gastrointestinal membranes (Fabs), the fraction of the absorbed dose that passes unchanged through the gut into the hepatic portal blood (F0) and the hepatic first pass availability (Fh) (Eq. 1)... 

Absorption barriers are related to the permeability of drug molecules across the gastrointestinal membrane including the colonic membrane. There are two distinct mechanisms for molecules to cross the membrane via paracellular transport and transcellular transport (Fig. 5). Para-cellular transport involves only passive diffusion where the molecules pass through the tight junctions between the epithelial cells. In contrast, transcellular transport can occur by passive diffusion as well as by active transport, or endocytosis. In general, the hydrophilic molecules diffuse predominantly through the paracellular route, whereas the lipophilic... 

The inclusion of a surfactant in the suppository formulation may enhance the rectal absorption of drugs. The effect has been attributed to the formation of mixed micelles. It has been suggested that the presence of the micelle facilitates the incorporation of the lipid component of the mixed micelle into the biological membrane. This lipid then enhances the fluidity and permeability of the membrane to the poorly absorbed drug. It appears that the colorectal mucous membrane is more sensitive to the effects of mixed micelles than the gastrointestinal membrane of the small intestine. 

Fisher, H., Seelig, A., Chou, R.C.andvande Waterbeemd, H. (1997) The difference between the diffusion through the blood-brain barrier and the gastrointestinal membrane. 4th International... 

The bioavailability of Class 111 compounds can practically not be influenced by a formulation. Rarely, the bioavailability can be improved by increasing the dose or by modifying the permeability of the gastrointestinal membrane. Modification of the gastrointestinal membrane structure by penetration or absorption enhancers always bears a safety risk because of also improving the uptake of all kind of toxins from the intestinal lumen and potentially causing severe irritations. What may be acceptable for an acute therapy may not be suitable for chronic treatment. 

Phenolic salts lodosubgallate Salicylate Subgallate Tribromophenate Tannate Internal astringent and absorbent for the protection of the gastrointestinal membrane. Used externally as an antiseptic. Treatment for gastroenteritis, toxic diarrhea, dermatitis, and hemorrhoids... 

This first pass phenomenon also exists after intraper-itoneal and, partially, after rectal administration. It does, of course, not exist for other routes of administration. Due to a hepatic first passage phenomenon, some drugs which are well absorbed through the gastrointestinal membrane still have a low bioavailability. 

The prevalent view is that the gastrointestinal membrane consists of a bimolecular lipoid layer that is covered on each side by protein with the lipid molecule oriented perpendicular to the cell surface (Fig. 9.4). The lipid layer is interrupted by small, water-filled pores with a radius of approximately 4 A, and a molecule with a radius of 4 A or less may pass through these water-filled pores. Thus, membranes have a specialized transport system to assist the passage of water-soluble material and ions through the lipid interior, a process sometimes termed to as convective absorption. The rate of permeation of such small molecules through the pore is affected not only by the relative sizes of the holes and the molecules but also by the interaction between permeating molecules... 

Lidocaine is widely used and is often the drug of choice for the acute treatment of ventricular arrhythmias. Although oral lidocaine readily penetrates the gastrointestinal membrane, it undergoes extensive first-pass metabolism, limiting its use to intravenous and intramuscular administration. ... 

Similar to the solid dosage forms containing chiral excipients, biological membranes may provide chiral environments (see Chapter 3). Most drugs cross the gastrointestinal membrane through simple passive diffusion thus, no stereoselectivity in the process is expected. It appears. 

For example amino acids, sugars and fatty acids will cross the membrane, while virtually no transfer of plasma proteins and certain toxins will occur. Figure 5.4 is a schematic of drug being absorbed across the gastrointestinal membrane. 

Figure 5.4 Drug absorption across the gastrointestinal membrane.

The gastrointestinal membrane separates the absorption site from the blood. Therefore, passage of drug across the membrane is a prerequisite for absorption. For this reason, drug must be in a solution form and dissolution becomes very critical for the absorption of a drug. The passage of... 

Equation 7.5 shows that the overall extent of bioavailability is the product of two factors reflecting the two steps involved in an orally administered drug reaching the systemic circulation first, traversing the gastrointestinal membrane and, second, surviving the first-pass effect in the liver. 

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