Oral administration gastrointestinal process

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 ...

Colchicine is rapidly absorbed after oral administration and tends to concentrate in the spleen, kidney, liver, and gastrointestinal tract. Leukocytes also avidly accumulate and store colchicine even after a single intravenous injection. Since colchicine can accumulate in cells against a concentration gradient, it is postulated that an active transport process may be involved in its cellular uptake. The drug is metabolized, primarily in the liver, by deacetylation. Fecal excretion plays a major role in colchicine elimination, since it and its metabolites are readily secreted into the bile. Only about 15 to 30% of the drug is eliminated in the urine except in patients with liver disease urinary excretion is more important in these individuals. 

Following oral administration, dissolution of the drug molecule in the intestinal milieu is a prerequisite for the absorption process. According to the Biopharmaceutical Classification System (BCS) [2], poor water-soluble compounds (i.e., aqueous solubility less than 100 pg/ mL) are class 2 or class 4 compounds. For class 2 compounds, the absorption level is dictated by the dissolution properties of the molecule in the gastrointestinal (GI) fluids. BCS class 4 compounds, which are characterized by both low solubility and poor intestinal wall permeability, are generally poor drug candidates (unless the dose is very low). 

Oral administration is the most popular route due to ease of ingestion, pain avoidance, versatility, (to accommodate various types of dmg candidates), and, most importantly, patient compliance [119]. In addition, solid oral delivery systems do not require sterile conditions and are, therefore, less expensive to manufacture. Orally delivered pharmacologically active compounds must have favorable absorption and clearance properties, and satisfactory metabolic stability to provide adequate systemic exposure to elicit a pharmacodynamic response. If the compounds possess reasonable physicochemical properties have low to intermediate clearance and reasonable absorption, adequate oral bioavailabdity may be achieved [120]. Indeed, oral bioavailability, defined as the rate and extent to which the active dmg is absorbed from a pharmaceutical form and becomes available at the site of dmg action [121], is influenced by several factors including solubility, permeability, intestinal and liver metabolism, rapid biliary and other efflux pump-mediated excretion, and conditions in the gastrointestinal milieu [122,123]. Thus, both absorption and elimination processes determine the oral bioavailability F of a given dmg. Accordingly, F can be estimated as... 

Fig. 2 Summary of processes involved following the oral administration of a drug in tablet or capsule form. (From Blanchard, J. Gastrointestinal absorption. II. Formulation factors affecting bioavailability. Am. J. Pharm. 1978, 150, 132-151.)...

Uptake of intact nanoparticulates from the gastrointestinal tract (GIT) after oral administration, for example, by endocytosis by the M cells of Payer s patches, is an area of controversy. Most research shows that the efficiency of this process is extremely low (much less than 1%), the extent is poorly defined and subject to great variability. Rather, it is the enhanced rate of dissolution of nanoparticulates which results in improved exposure. ... 

Fa is the fraction of dose absorbed into enterocytes from the intestinal lumen after oral administration. The two major processes involved are (1) the dissolution of solid particles into gastrointestinal (GI) fluid and (2) the permeation of molecules across intestinal membranes. 

Oral administration The oral route is the most common way of administering a drug. For a drug to be absorbed into the bloodstream, it has to be soluble in the fluids of our gastrointestinal tract. Drugs are often formulated with excipients (components other than the active drug) to improve manufacturing and dissolution processes (see Section 5.5). 

Although oral administration is the preferred delivery route for the majority of drugs, the complexity of the gastrointestinal (GI) tract needs to be considered. Figure 8.10 shows the GI tract with the processes that can occur which affect a drug at various stages during transit. 

Intravenous Administration When a drug is injected, the entire dose can be considered as being available in the bloodstream to be distributed to the target site. Hence, the dosage can be controlled, unlike with other routes of administration, where the bioavailability of the drug may be unpredictable because of diffusion processes. Intravenous injection is the normal route for administration of protein-based drugs, as they are likely to be destroyed if taken orally because of the pH conditions in the gastrointestinal tract. 

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