Gastrointestinal tract drug passage

Once absorbed from the gastrointestinal tract, drugs pass through the liver via the portal circulation and are metabolized to various extents (the first-pass effect). Following passage through the liver, the drugs are distributed to the tissues by the systemic circulation. 

A number of the water-soluble polymers also have adhesive properties which are being extensively evaluated for drug delivery (9). These polymers will adhere to the mucous coating in the gastrointestinal tract, the nose, and the mouth to delay passage and sustain drug release. Those polymers with the best adhesive properties are those with hydroxyl and carboxyl groups. Table II lists some of the bioadhesive polymers and their adhesive properties. 

Because the entire blood supply of the upper gastrointestinal tract passes through the liver before reaching the systemic circulation, a drug may be metabolized by the gut wall and the liver during its first passage of drug... 

Because most proteins are susceptible to protease degradation and denaturation in biologic fluids, most biopharmaceuticals must be administered by intravenous, intramuscular, or subcutaneous injection (see Table 5.5). High concentrations of proteases are found in the gastrointestinal tract, nasal mucosa, bronchioles, and alveoli, which severely limit the bioavailability of protein pharmaceuticals after oral, intranasal, and inhalation administration. Diffusional barriers to the passage of relatively large macromolecules preclude transdermal and mucosal administration of protein pharmaceuticals. Research is under way to develop methods that will protect protein drugs from proteolysis and improve transmembrane diffusion. 

Normally, drugs reach their target organ via the blood. Therefore, the drug molecules first have to enter the circulation, which requires the passage through barrier membranes in the gastrointestinal tract. This process is called resorption or absorption. 

The purpose of this chapter is to document the nature of the enzyme barrier that macromolecular drugs will encounter during their passage down the human gastrointestinal tract. I will discuss the peptidases that digest peptides and proteins and the nucleases that will hydrolyse nucleic acids and also briefly consider other enzymes that may affect the behaviour of the newer generation of pharmaceutical formulations. It is very important to consider both the qualitative aspects of the problem, that is, the specificity of the digestive... 

Drug properties that are important to consider during development of IR tablets are metabolism, stability, permeability, and solubility [18,19]. In the development of ER formulations, these aspects are also important, but in addition to IR formulations, they must be considered in relation to the different environments that the ER formulations meet during their passage through the gastrointestinal tract, and some of these aspects will be discussed briefly below. It can be mentioned that, based on these initial properties for drug candidates, Thrombre has constructed a feasibility assessment flow chart for ER formation development [18]. 

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