Free drug fraction vs free drug concentration: a matter of frequent confusion.

In plasma, alteration of drug binding results in a decrease (or an increase) in the unbound fraction of a drug and thus in a reduced (or increased) effect. This classical sentence encountered in numerous articles on veterinary pharmacology is almost invariably wrong. It stems from a major confusion between two variables: the free fraction of a drug in plasma (fu) and its free plasma concentration (Cfree). For most drugs, effects are governed by free drug concentrations and therefore can be altered by factors which modify the free drug concentration, which is not equivalent to changing the free drug fraction, as explained in this note.