plasma protein binding

Imagine the bloodstream as a busy harbour where large protein 'ferries' float about. Many drug molecules climb aboard these proteins and ride along, temporarily out of action. Plasma protein binding is this reversible attachment of drug to blood proteins, and it controls how much drug is actually free to do its job.

Only the unbound fraction can leave the capillaries, reach receptors, be filtered by the kidney or be metabolised by the liver. The bound fraction acts as a circulating, instantly available depot: as free drug is used up, bound drug detaches to replace it. Acidic drugs (such as warfarin and many NSAIDs) bind mainly to albumin, while basic drugs (such as lidocaine and many antipsychotics) bind to alpha-1-acid glycoprotein.

The degree of binding matters most for highly bound drugs. If a drug is 99 percent bound, a small change in binding can double the free, active fraction. Binding can fall in conditions like low albumin (liver disease, malnutrition) or when a second drug competes for the same site, potentially altering effect and toxicity.