Drug distribution is a very complex process, and therefore many factors can influence the movement of the drug in the body. These are predominantly physiological factors and govern rate and extent of distribution. The rate can be influenced by absorption and blood perfusion of the drug. The extent can be affected by lipid solubility, plasma protein binding, tissue protein binding, pH–pKa of the drug .
Cell membranes, which are made up of phospholipids, form the main barriers between the compartments in the body. Lipid soluble drugs pass through lipidic cell walls very easily. The movement of water-soluble drugs depends on the passive transport which happens slowly, and the rate is dependent on drug molecule size. The highly profuse organs tend to receive the major part of total drug molecules present in the systemic circulation. In addition to this, the nonionic form of the drug has higher lipid solubility and, in turn, better permeability in a different compartment of the body. An ionic or nonionic form of the drug depends on pKa. Variation in the pH in different body compartments plays an important role in drug disposition and accumulation of drugs in specific compartments. This aspect is well explored for target delivery of many anticancer drugs to tumor sites.