LAUSR

ABSTRACT Introduction: Given that membrane efflux transporters can influence a drug’s pharmacokinetics, efficacy and safety, identifying potential substrates and inhibitors of these transporters is a critical element in the drug discovery and development process. Additionally, it is important to predict the inhibition potential of new drugs to avoid clinically significant drug interactions. The goal of preclinical studies is to characterize a new drug as a substrate or inhibitor of efflux transporters. Areas covered: This article reviews preclinical systems that are routinely utilized to determine whether a new drug is substrate or inhibitor of efflux transporters including in silico models, in vitro membrane and cell assays, and animal models. Also included is an examination of studies comparing in vitro inhibition data to clinical drug interaction outcomes. Expert opinion: While a number of models are employed to classify a drug as an efflux substrate or inhibitor, there are challenges in predicting clinical drug interactions. Improvements could be made in these predictions through a tier approach to classify new drugs, validation of preclinical assays, and refinement of threshold criteria for clinical interaction studies.