Drug Distribution

This chapter provides a context for understanding drug distribution into tissues and addresses those factors that play a major role in determining the rate and extent of drug distribution. Transporters can greatly facilitate the passage of a drug from one side of a biological membrane to the other. The orientation of transporters is either apical or basolateral and these terms also are referred to as luminal or abluminal, respectively. Drug movement across barrier-forming biological membranes can generally be accomplished by three mechanisms. Carrier-mediated transport is the most prevalent mechanism because it affords greater control as to the type and quantity of molecules that can be translocated. Passive diffusion is a major process by which drugs cross cell membranes. The cell bilayer, which is permeable to lipophilic molecules and favors their partitioning into the membrane, represents an important first step in flux across the membrane. Most drugs leave the site of absorption and distribute to sites of action and elimination by traveling in the blood. Distribution concepts need to consider the limitations of this physiological reality. © 2009