In Vitro Characterization of Interactions with Drug Transporting Proteins

In vivo, drugs that are substrates of transport proteins often interact with more than one transporter and may also be substrates of drug metabolizing enzymes. This complexity makes in vivo observations of potential transporter interactions difficult to interpret, and, as a result of this, most transporter interactions have been identified using controlled conditions in in vitro models. In this chapter, we review in vitro characterization of DDIs with transport proteins and, more specifically, for transporters that have been shown to have significant clinical effects. The focus will be on interactions taking place at the organ barriers known to influence pharmacokinetics in man. We will cover in vitro models used, methods for predicting DDIs with transport proteins, and the substrates and inhibitors recommended for use in such studies. We also exemplify how in vitro studies have been used to identify, predict, or explain transporter-mediated DDIs and comment upon how recent findings, e.g., quantitative proteomics, improve the in vitro predictions of the interactions.