The clinical significance of the changing of plasma protein binding of drug was discussed. Blood concentration of free drug equilibrated with that at the site of action can be used as a useful tool for monitoring pharmacotherapy. The significant increase of blood concentration of free drug may be produced in a very restricted case which is described in detail in this article. However, it should be emphasized that the changing of concentration of total drug in blood does not parallel with that of free drug. Although the changing of plasma protein binding seems to be a minor factor in most of clinical cases, we should notice the role of protein binding which covers the changing of free drug when the monitoring using total drug concentration is performed.
