What is the true clinical significance of plasma protein binding displacement interactions ?

In this article, we demonstrate why plasma binding displacement rarely leads to alterations in the clinical effects of a drug, and why drug-drug interactions involving alterations in absorption, hepatic metabolism or renal excretion are of far greater importance. We also identify the types of drugs for which plasma protein binding displacement may be important clinically, and demonstrate why an understanding of the in vivo consequences of displacement is essential for the appropriate interpretation of therapeutic drug monitoring and clinical pharmacokinetic data.