Distribution of Drugs

• Distribution is the reversible transfer of a drug from the bloodstream to various tissues and organs.
• Once absorbed, drugs distribute throughout the body, moving into different tissues and fluids.

Distribution depends on:

1. Blood Flow (Perfusion Rate)

   • Organs with higher blood flow (brain, liver, kidneys) get drug supply more rapidly.
   • Skeletal muscle, adipose tissue, and skin receive the drug more slowly.

2. Plasma Protein Binding

   • Many drugs bind to albumin (acidic drugs) or α1-acid glycoprotein (basic drugs).
   • Bound drugs are not free to exit capillaries or exert a pharmacological effect; only unbound (free) drug is active.
   • Protein binding is reversible, and changes in binding (e.g., due to hypoalbuminemia, displacement by other drugs) can alter the free drug concentration.

3. Tissue Binding

   • Drugs can accumulate in certain tissues (fat, bone, muscle) due to various affinities.
   • Example: Tetracyclines accumulate in bones and teeth because they bind to calcium.

4. Specialized Barriers

   • Blood-Brain Barrier (BBB): Tight junctions in the cerebral endothelium limit penetration to more lipophilic drugs or those using specific transport mechanisms.
   • Placental Barrier: Less selective than the BBB, yet still restricts some drugs; many cross, so fetal drug exposure is a concern.

5. Volume of Distribution (Vd)

   • A theoretical volume that relates the amount of drug in the body to the concentration of drug in the blood/plasma.
   • If a drug has a high Vd, it indicates extensive distribution into tissues.
   • A low Vd indicates the drug is largely contained in the vascular compartment.

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