Gastrointestinal tract absorption process

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. 

Figure 8.10 Gastrointestinal tract with processes affecting drug absorption efficiency.

Chemicals have to pass through either the skin or mucous membranes lining the respiratory airways and gastrointestinal tract to enter the circulation and reach their site of action. This process is called absorption. Different mechanisms of entry into the body also greatly affect the absorption of a compound. Passive diffusion is the most important transfer mechanism. According to Pick s law, diffusion velocity v depends on the diffusion constant (D), the surface area of the membrane (A), concentration difference across the membrane (Ac), and thickness of the membrane (L)... 

The gastrointestinal tract (GIT) is a highly specialized region of the body whose primary functions involve the processes of secretion, digestion, and absorption. Since all nutrients needed by the body, with the exception of oxygen, must first be ingested orally, processed by the GIT, and then made available for absorption into the bloodstream, the GIT represents a significant barrier and interface with the environment. The primary defense mechanisms employed by the gut... 

Delivery of either a small or large dose of the drug at the same rate Delivery of drug at the intended site of absorption irrespective of the region of the gastrointestinal tract where that process occurs... 

In the enterocyte as it enters the absorptive zone near to the villus tips, dietary iron is absorbed either directly as Fe(II) after reduction in the gastrointestinal tract by reductants like ascorbate, or after reduction of Fe(III) by the apical membrane ferrireductase Dcytb, via the divalent transporter Nramp2 (DCT1). Alternatively, haem is taken up at the apical surface, perhaps via a receptor, and is degraded by haem oxygenase to release Fe(II) into the same intracellular pool. The setting of IRPs (which are assumed to act as iron biosensors) determines the amount of iron that is retained within the enterocyte as ferritin, and that which is transferred to the circulation. This latter process is presumed to involve IREG 1 (ferroportin) and the GPI-linked hephaestin at the basolateral membrane with incorporation of iron into apotransferrin. (b) A representation of iron absorption in HFE-related haemochromatosis. 

There are many prevalent conditions in the elderly that can interfere with the normal pharmacokinetic process. The changes in the gastrointestinal tract due to aging do not normally give any problems with drug treatment but in combination with diverse chronic ailments, they do. The absorption of drugs can be disturbed by the... 

Figure 2.1 Oral drag absorption process from the gastrointestinal tract (GIT). Schematic depicting the three major processes (/a, / and /h) affecting absorption of drug from the site of administration to the systemic circulation, that is oral bioavailability, /a- fg, and /h can be estimated from the general relationship provided in Eq. 2.3 ...

The in vivo absorption process is the outcome of a complex series of events and depends on a multitude of parameters related to drug characteristics as well as to physiological aspects of the gastrointestinal (GI) tract [93], A summary of the most important factors influencing the rate and extent of intestinal absorption is given in Table 8.1. 

The basis for all CAT models is the fundamental understanding of the transit flow of drugs in the gastrointestinal tract. Yu et al. [61] compiled published human intestinal transit flow data from more than 400 subjects, and their work showed the human mean small intestinal transit time to be 199 min. and that seven compartments were optimal in describing the small intestinal transit process using a compartmental approach. In a later work, Yu et al. [58] showed that between 1 and 14 compartments were needed to optimally describe the individual small intestine transit times in six subjects but in agreement with the earlier study, the mean number of compartments was found to be seven. This compartmental transit model was further developed into a compartmental absorption and transit (CAT) model ([60], [63]). The assumptions made for this CAT model was that no absorption occurs in the stomach or in the colon and that dissolution is instantaneous. Yu et al. [59] extended the CAT model... 

Another important advance adding to the value of PBPK modeling in the pharmaceutical industry are physiological, mechanistic models developed to describe oral absorption in humans and preclinical species. Oral absorption is a complex process determined by the interplay of physiological and biochemical processes, physicochemical properties of the compound and formulation factors. Physiologically based models to predict oral absorption in animals and humans have recently been reviewed [18, 19] and several models are now commercially available. The commercial models have not been published in detail because of proprietary reasons but in essence they are transit models segmenting the gastrointestinal tract... 

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