Drug Absorption: Overview

Drug absorption varies by route. Intravenously injected drugs directly enter systemic circulation immediately. Orally administered drugs travel through the gastrointestinal tract, where intestinal villi rich in blood supply provide a large surface area for absorption. Drugs then passively diffuse or use transporters to cross the intestinal cell membrane and enter the bloodstream.

Drug physicochemical properties critically determine absorption efficiency. Nonionized and lipophilic drugs are readily absorbed, while less lipophilic drugs like strong acids or bases are poorly absorbed in the gut. The drug's ionization state, influenced by pH at the absorption site, affects its ability to cross the intestinal cell membrane and reach the bloodstream.

For solid drugs, the rate of dissolution directly limits absorption. A drug must dissolve before it can be absorbed across the intestinal membrane. Slower dissolution rates reduce the amount of dissolved drug available for absorption, thereby decreasing the overall bioavailability and therapeutic effectiveness of the medication.

Gastrointestinal motility significantly impacts drug absorption. Gastric stasis, which slows stomach emptying, or rapid gut content movement can impair absorption by altering the time a drug spends in contact with the intestinal epithelium. These changes affect how much drug dissolves and crosses the intestinal membrane into the bloodstream.

Drugs cross intestinal membranes through multiple mechanisms. Most drugs passively diffuse across the membrane, while others actively use specific transporters or facilitated diffusion, which remains passive but carrier-mediated. These mechanisms, collectively called mechanisms of drug absorption paracellular transcellular and vesicular transport, determine how efficiently drugs enter the bloodstream.

Bioavailability, the fraction of administered drug reaching the bloodstream as intact drug, is reduced by multiple factors. Not all drug dissolves, some fails to cross the intestinal membrane, and some may be metabolized before absorption. Additionally, factors like gut motility, pH, and drug properties collectively determine what percentage of the total dose actually enters systemic circulation.

The intestine is highly effective for drug absorption due to its specialized anatomy. Intestinal villi are rich in blood supply and provide an enormous surface area for drug contact and absorption. This extensive vascularization and large epithelial surface enable efficient transfer of absorbed drugs directly into the bloodstream for systemic distribution.