• Drug Absorption II Continued

  • Aqueous Diffusion

    • Aqueous diffusion of drugs is associated with large aqueous compartments such as the interstitial space and the cytosol.^12,19 

      • In addition, aqueous diffusion describes drug movement across epithelial membrane tight junctions as well as endothelial cells that line blood vessels by means of aqueous pores.

        • Under some circumstances relatively large molecules (molecular weight ~25,000) may pass through these pores.

        • Aqueous diffusion is one type of passive diffusion.

          • Lipid diffusion is the other type of passive diffusion.

          • Passive diffusion represents the most common and simplest mechanism for drug absorption, depending only on a concentration gradient.^15,19

            • The most common mechanism for drug passage across membranes is passive diffusion, which follows Fick's law of diffusion.²¹ 

              • Lipophilic drugs readily dissolve in the lipid bilayer and diffuse across the membrane down their concentration gradient.

              • The rate of diffusion depends on the drug's lipid-water partition coefficient.

              • Small, unionized molecules cross membranes more readily than large, ionized species.

          • As noted earlier, Fick's law (of diffusion) describes passive diffusion in which drug molecules move from regions of higher to lower concentration.

          • Aqueous diffusion describes movement of non-protein bound drugs as drugs associated with large plasma proteins e.g. albumin are not able to penetrate most aqueous pores.

            • Drugs which carry a charge may have transport influences by local electric fields, such as the nephron's transtubular membrane potential.¹²

  • Lipid Diffusion¹²

    • The diffusion of drugs through the lipid region of the membrane bilayer represents the central limiting factor to the drug reaching its site(s) of action.

      • This conclusion is based on the numerous lipid barriers which separate body compartments.

      • The lipid: aqueous partition coefficient described previously predicts how easily a drug moves between aqueous and lipid regions.

Updated June 2025

References