Physiological and Physical Factors Governing the Initial Stages of Drug Distribution

Abstract

The distribution of a drug, like that of any molecular species introduced into the organism, depends upon a complex series of physical and chemical processes which are often interrelated. These processes take up and dilute the substance at its site of entry, carry it to the various body tissues, permit it to diffuse or actively transport it across several membranes, and determine its accumulation and disposition by the tissues. More specifically, the concentration of a substance thus introduced depends, over time, on the history of its concentration in the arterial blood, the rate at which blood passes through each tissue, the physical processes occurring there (e.g., diffusion and solubility), and the chemical processes of active transport, binding, and metabolism. My interest in these processes began nearly 30 years ago and arose, not so much from a desire to understand the distribution of drugs, as from an interest in deriving from the distribution of a suitable tracer, a measurement of the physiological functions involved. The problem was to describe the tissue distribution of such a foreign substance in terms of physiological parameters rather than empirical constants and precisely enough to derive the physiological function from the distribution.