Drug Distribution

Once in systemic circulation, the drug molecules will extravasate to other tissues, including the targeted organ(s), a process that we will refer to as drug distribution. Pharmacologically speaking, drug distribution is a critical process since it determines a) the drug concentration at its site of action at a given time point and b) the amount of drug that reaches other tissues different from the site of action. The pattern of drug distribution also influences the elimination half-lives of drugs and, therefore, the extent of their action. The extent and rate of drug distribution depend on several factors such as physiochemical properties of the drug, vascular permeability, cardiac output, regional blood flow, the ability of the drug to bind plasma proteins and tissue elements, and pH partition. Besides discussing such factors, this chapter will briefly introduce the concepts of real and apparent volumes of distribution, and some experimental approximations to determine the fraction bound to plasma proteins.