Oral Drug Absorption & Bioavailability (F)

For a drug to permeate a membrane, it must first be in solution. This doesn't necessitate the administration of the drug in a solution form but indicates the need for solubilization to facilitate absorption. The body's systemic circulation acts as a sink to maintain concentration gradient, effectively pumping the absorbed drug away from the absorption site. This mechanism maintains a low concentration at the absorption site, thereby encouraging further drug absorption down the concentration gradient. After oral administration, the stomach serves as the initial site for absorption. Due to the stomach's acidic pH, acids are better absorbed here than bases. Acids remain primarily in their unionized form in this environment, enabling easier permeation through cell membranes. However, all drug types, whether acidic, basic, or neutral, are most effectively absorbed in the small intestine to be a more effective absorption site than the stomach. This is attributed to the small intestine's larger surface area and greater perfusion, which together facilitate a higher rate of drug absorption. Moreover, the permeability of intestinal membranes surpasses that of the stomach's, aiding both acidic and basic drugs.

Several factors can impact drug absorption in the GI system. Consuming certain foods, especially those high in fat, as well as specific drugs like some antidepressants, opioids, and antihypertensives, can decelerate gastric emptying, leading to a reduced drug absorption rate. Factors such as the decreasing surface area from the duodenum to the rectum and tighter epithelial spaces in the colon further diminish drug absorption. The molecular weight of a drug also plays a role--drugs weighing over 350 g/mol have diminished permeability. Yet, certain transport mechanisms, like facilitated transport using uptake transporters (PEPT1, OATP3), can enhance absorption for drugs like amoxicillin and gabapentin which might otherwise face poor oral absorption. Conversely, efflux transporters, like Pgp, can reduce systemic absorption by transporting drug molecules back into the intestinal lumen. A significant factor in drug absorption is the transit time through the intestines, which at ~4 hours, may be insufficient for some drugs. The oral bioavailability (F) equation, FA x FG x FH, is useful in understanding the fraction of drug that successfully navigates each absorption step. Some drugs face the first-pass effect following oral absorption, being metabolized as they pass through intestinal tissues and into the liver. Drugs with poor oral absorption or those subjected to extensive metabolism might be more suitably administered parenterally (e.g IV).