[The pharmacokinetic process: is the drug getting to its site of action?: Drug distribution (ADME)].

Many drugs are bound to circulating proteins, usually albumin (acidic drugs), but also globulins (hormones), lipoproteins (basic drugs), and acid glycoproteins (basic drugs). Only the fraction of drug that is not protein-bound can bind to cellular receptors, pass across tissue membranes, and gain access to cellular enzymes, thus being distributed to body tissues, metabolized, and excreted (for example by the kidney). Changes in protein binding can therefore sometimes cause changes in drug distribution. For such changes to be important, the bound drug must constitute more than 90% of the total drug in the plasma and possess a reduced therapeutic window Besides this, the extent of distribution of the drug to the tissues must be small (less than 0.15 L/kg). This is because if the drug is widely distributed to the body tissues, then even large increases in the amount of unbound drug in the plasma will be unimportant.