Usually reversible

Determins volume of distribution (Vd)

Slows drug metabolism and excretion

prolongs the duration of action (t1/2)

results in clinically important drung interactions

Many drugs circulate in the bloodstream bound to plasma proteins.

certain drugs may bind to proteins that function as specific hormone carrier proteins

the drugs bound to plasma proteins cannot diffuse from the vascular space and is pharmacologically inactive, the unbound portion of a drug is pharmacologically active.

Binding of a drug to plasma proteins limits its concentration in tissues and at its site of action because only unbound drug is in equilibrium across membranes.

Binding of a drug to plasma protein limits the drug’s glomerular filtration and may also limit drug transport and metabolism.

The fraction of total drug in plasma that is bound is determined by 3 factors

The extent of plasma protein binding also may be affected by: disease-related factors (e.g., hypoalbuminemia). Conditions resulting in the acute-phase reaction response (e.g., cancer, arthritis, myocardial infarction, Crohn’s disease)

A more common problem resulting from competition of drugs for plasma protein-binding sites is misinterpretation of measured concentrations of drugs in plasma

Binding of drugs to plasma proteins is a non selective and many drugs can compete these binding sites leading to serious drug interactions.

Examples of drugs with high PP binding capacity

Examples of drugs interactions

Quinidine has higher TPB capacity than digoxin.

If Quinidine given to patients who are receiving digoxin, the plasma concentration of free digoxin is highly increased because Quinidine displaces digoxin from tissue binding sites (it also displaces digoxin from plasma protein binding sites)

It impairs the renal excretion of digoxin). This can lead to serious digoxin toxicity

Bound form of drugs

Unbound form of drugs

Many drugs accumulate in tissues at higher concentrations than those in the extracellular fluids and blood.

Tissue binding of drugs is like plasma protein binding and it is usually occurring with tissue proteins.

Tissue binding of drugs usually occurs with cellular constituents such as proteins, phospholipids, or nuclear proteins.

A large fraction of drug in the body may be bound in this fashion and serve as a reservoir that prolongs drug action in that same tissue or at a distant site reached through the circulation.

Such tissue binding and accumulation also can produce local toxicity

It is generally a reversible and competitive process.

Displacement of drugs from tissue binding sites is a mechanism for drug interaction.