Tissue permeability refers to the ability of drugs to cross cell membranes and enter tissues, influencing drug distribution and therapeutic action.
It depends on both drug properties and physiological barriers.
Factors Influencing Tissue Permeability
1) Lipid Solubility
Lipid-soluble drugs easily diffuse through the lipid bilayer of cell membranes.
Water-soluble drugs require transporters or channels to cross membranes.
2) Molecular Size and Shape
Smaller, more compact molecules pass through membranes more easily than larger, bulkier ones.
3) Charge
Charged molecules may need specific transporters or channels, while uncharged molecules can diffuse more readily.
4) Ionization State
The pH of the surrounding environment influences a drug’s ionization, affecting its ability to cross membranes.
Acidic drugs tend to accumulate in acidic tissues (e.g., stomach), while basic drugs accumulate in basic tissues (e.g., liver).
5) Protein Binding
Many drugs bind to plasma proteins (e.g., albumin), reducing their availability for tissue distribution.
Only unbound (free) drugs are available for active transport into tissues.
6) Blood Flow
Highly perfused organs (e.g., liver, kidneys, brain) receive drugs more rapidly than low-perfusion tissues (e.g., adipose tissue).
7) Capillary Permeability
The permeability of capillaries influences how easily drugs enter tissues.
Some tissues, such as the brain, have highly selective barriers, while others, like the liver, allow easier drug passage.
