An Extended Model Including Target Turnover, Ligand-Target Complex Kinetics, and Binding Properties to Describe...

Since the beginning of this century, target-mediated drug disposition has become a central concept in modeling drug action in drug development. It combines a range of processes, such as turnover, protein binding, internalization, and non-specific elimination, and often serves as a nucleus of more complex pharmacokinetic models. It is simple enough to comprehend but complex enough to be able to describe a wide range of phenomena and data sets. However, the complexity comes at a price: many parameters. In this chapter, we present an overview of the temporal development of the compounds involved after different types of drug doses and offer convenient handles for dissecting data sets in a sophisticated manner in order to estimate the values of these parameters, such as rate constants and pertinent concentrations.