Paracellular transport depends primarily on which property of the drug?

• A. pH of surroundings
• B. Molecular weight of the drug
• C. Presence of enzymes
• D. Temperature

Answer: (B)

Paracellular transport happens through the tight junctions between neighboring epithelial cells, in an aqueous pore that favors small, hydrated molecules. The main factor that determines whether a drug can squeeze through these intercellular spaces is its size, i.e., molecular weight. Smaller molecules can diffuse through the pore more readily, while larger ones are restricted, making molecular weight the best predictor for this route.

pH mostly influences how a drug ionizes, which affects its ability to cross membranes via the transcellular route rather than through the tight junctions. The presence of enzymes relates to metabolism rather than the physical size limitations of the paracellular pathway. Temperature can alter the rate of diffusion in general, but it does not change the intrinsic capacity of the aqueous paracellular pore to admit a molecule; the size of the molecule remains the determining factor.