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:
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.
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.
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.
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.
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.