3.8
Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport
Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial…
After administration, drugs must cross cell membranes to reach their target site in the body. For example, oral drugs must navigate intestinal epithelial membrane barriers to enter the systemic circulation.
Drugs with a molecular weight lower than 500 Daltons bypass cell membranes and take the paracellular route. They diffuse through the gaps between neighboring cells.
Most drugs prefer the transcellular route to directly traverse through the cell membranes via two distinct mechanisms.
Passive transport allows drugs to pass freely through the lipid bilayer along the concentration gradient.
Active transport, on the other hand, utilizes membrane transporters, and ATP to move drugs against the concentration gradient. In some cases, drugs are exchanged for other solutes which are moving along their concentration gradient.
Lastly, vesicular transport involves the cell membrane invagination to internalize large macromolecules, insoluble or soluble particles inside the cell. Engulfment of macromolecules or large foreign particles is termed phagocytosis, whereas internalization of fluids containing small particles is pinocytosis.
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Q1: What is the paracellular route and which drugs use it?
The paracellular route allows drugs to diffuse through gaps between neighboring cells without crossing the cell membrane itself. Drugs with a molecular weight lower than 500 Daltons typically use this pathway because their small size enables them to bypass cell membranes entirely and move along the concentration gradient between adjacent epithelial cells.
Q2: How does passive diffusion differ from active transport in drug absorption?
Passive diffusion allows drugs to move freely through the lipid bilayer along the concentration gradient without requiring energy. Active transport, conversely, uses membrane transporters and ATP to move drugs against the concentration gradient, enabling cells to absorb drugs even when their concentration is lower inside the cell than outside.
Q3: What are symport and antiport mechanisms in secondary active transport?
In secondary active transport, drugs are exchanged for other solutes moving along their concentration gradient. Symport involves simultaneous movement of both substances in the same direction, while antiport moves them in opposite directions. Both mechanisms allow cells to transport drugs against their electrochemical gradient without directly consuming ATP.
Q4: Why must oral drugs cross intestinal epithelial barriers?
Orally administered drugs must traverse intestinal epithelial membrane barriers to enter the systemic circulation and reach their target sites throughout the body. Without crossing these barriers, drugs remain in the gastrointestinal tract and cannot exert therapeutic effects on distant tissues or organs.
Q5: What is the difference between phagocytosis and pinocytosis?
Phagocytosis is the engulfment of large foreign particles or macromolecules by the cell membrane, often called cell eating. Pinocytosis, or cell drinking, involves internalization of fluids containing small particles. Both are forms of vesicular transport where the cell membrane invaginates to bring materials into the cell.
Q6: How does molecular weight affect drug absorption pathways?
Molecular weight determines which absorption route a drug can use. Drugs below 500 Daltons can use the paracellular route by diffusing through intercellular gaps. Larger drugs must use transcellular transport through cell membranes via passive or active mechanisms, or rely on vesicular transport for macromolecules and insoluble particles.
Q7: What role do membrane transporters play in drug absorption?
Membrane transporters are essential proteins that facilitate active transport, allowing cells to move drugs against concentration gradients using ATP energy. These transporters enable selective, energy-dependent absorption of specific drugs, making active transport more efficient than passive diffusion for certain pharmaceutical compounds that require carrier-mediated mechanisms.