Tissue Permeability of Drugs

Tissue Permeability of Drugs depends on lipid solubility, ionization, molecular size, and membrane transport mechanisms.

• 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.

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