Drug Distribution

Abstract

Once a drug enters the bloodstream, it will be carried by the blood to various parts of the body. In order for it to act on its target site(s) of action, the drug must leave the bloodstream to which it may later return. Such reversible transfer of substances between the blood and extravascular tissues is known as distribution. Distribution generally occurs rapidly for most drugs and is often much faster than elimination. How widespread a drug action is often depends on its distribution profile. Its ability to distribute to specific tissues depends on both physiological factors (e.g., tissue perfusion, membrane permeability) and drug properties (e.g., molecular size, degree of ionization, lipid solubility, relative binding to plasma protein and tissue protein). The volume of distribution (V_d) is the second most important pharmacokinetic parameter after plasma clearance (CL). It gives some idea as to the extent of distribution of a drug in the body. It also determines the loading dose (D_L) to be given during multiple dosing in order to achieve plasma steady-state concentration (C_ss) faster. Factors that alter the distribution of a drug (e.g., edema, sepsis, pregnancy) may contribute to failure in achieving the expected clinical outcome.