drug distribution
Once a drug enters the bloodstream, it does not simply stay there waiting to act. Like water poured into a house with many rooms, it seeps out of the blood and spreads into muscles, fat, organs and other tissues. Drug distribution is this reversible movement of drug back and forth between the blood and the various body compartments.
Distribution is driven by blood flow to each tissue, the ability of the drug to cross cell membranes, and how strongly the drug binds to proteins in plasma versus components inside tissues. Well-perfused organs such as the brain, heart, liver and kidney receive drug first; poorly perfused tissues such as fat and resting skeletal muscle fill up more slowly. Only the unbound, free drug can actually leave the blood and reach its target.
Distribution is a separate step from absorption (getting in) and elimination (getting out), but it overlaps with both in time. A drug that distributes extensively into tissues may show low blood concentrations yet still be present in large amounts in the body, which has important consequences for dosing and for interpreting plasma drug levels.
Thiopental, an intravenous anaesthetic, distributes rapidly into the brain to induce sleep within seconds, then redistributes into muscle and fat, ending its effect within minutes even though much drug remains in the body.
Fast distribution followed by redistribution shapes the clinical effect.
Distribution is the D in ADME. It is reversible: drug that has moved into tissue can move back into blood as plasma concentration falls.