Factors Affecting Drug Distribution: Tissue Permeability

Drug distribution across biological membranes to target tissues relies on the drug's physicochemical properties, such as molecular size, ionization degree, partition coefficient, and stereochemical nature.

For instance, small molecules can easily permeate the capillary membrane, while larger molecules require specialized transport systems.

Unionized, lipophilic drugs cross cell membranes rapidly, whereas ionized, polar, and hydrophilic drugs cannot.

Blood pH changes resulting from acidosis or alkalosis can alter drug ionization, impacting intracellular concentration.

For instance, in barbiturate poisoning treatment, sodium bicarbonate induced alkalosis increases drug ionization, which prevents further CNS entry. This drives the drug out, enhancing urinary excretion.

A polar drug's distribution is influenced by its effective partition coefficient. For instance, thiopental, a weak acid with a high partition coefficient, distributes more rapidly than salicylic acid, a strong acid with a lower coefficient.

Furthermore, a drug's stereochemical nature, particularly when interacting with macromolecules like proteins, can affect its distribution.