Distribution

The better to understand distribution, it is easier to consider the body as consisting of five main compartments: the plasma, interstitial fluid, intracellular and lymph fluid, transcellular fluid and body fat. Generally, women have less water and more fat then men. How drugs distribute between these compartments is dependent on how lipid-soluble the drug is. The more lipid-soluble the compound the more it will distribute in all compartments and may accumulate in fat. The blood-brain barrier is a particularly important entity, and consists of a continuous layer of endothelial cells, joined by tight junctions that ensure that the brain is inaccessible to most compounds, and particularly to poorly lipid-soluble drugs.

Once absorbed, most drugs are distributed in the plasma, either bound to proteins or in 'free' form. Drug molecules that are free are able to move out of the plasma across a cellular barrier towards their target sites. The volume of distribution (Vd) is a theoretical measure used to demonstrate how a drug is distributed. It is defined as the volume of plasma that would contain the total body content of the drug at a concentration equal to that in the plasma. The larger the Vd, the more likely the drug is to accumulate outside the plasma.

Understanding how a drug is distributed can allow one to be able to understand better how well a drug will reach its target site. Distribution can vary greatly between individuals and in certain cases: for example, the volume of distribution is increased in pregnancy.

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