Free drug theory

Abstract

The free drug theory (sometimes also termed free drug hypothesis) provides a conceptual framework increasingly used to understand pharmacokinetics/pharmacodynamics (PK/PD) relationships [1]. It underlines the central role of free (or unbound) drug concentration at the site of action (the surroundings of the drug target) as determinant of in vivo efficacy and pharmacokinetics. A deep understanding of this theory can also be helpful to establish in vitro-in vivo correlations or, alternatively, to provide explanations to absence of clear correlations between in vitro and in vivo studies.