Drug Absorption Mechanism: Passive Membrane Transport

In drug absorption via passive transport, small lipid-soluble drugs traverse by diffusion across the cell membrane down the concentration gradient.

The rate of transfer is directly proportional to the drug's lipid–water partition coefficient. The greater the partition coefficient, the more lipid-soluble is the drug, and the more rapid is its diffusion.

Most drugs are weak acids or weak bases. The lipid-insoluble ionized species do not permeate the membrane, while the lipid-soluble nonionized forms diffuse readily.

The transmembrane distribution of a drug depends on the pK_a of the drug and the pH gradient across the membrane.

For instance, consider a weakly acidic drug dissolving in the gastric juice of the stomach.

In the gastric compartment, the drug remains primarily undissociated because its pK_a is higher than the pH,  and this form diffuses easily across the barrier.

In the plasma, where the drug's pK_a is lower than the pH, the drug readily dissociates. Furthermore, because the ionized form of the drug cannot diffuse through the barrier, this form predominates in the plasma.