Background: ABCB1 is a key ABC efflux transporter modulating the pharmacokinetics of a large percentage
of drugs. ABCB1 is also a site of transporter mediated drug-drug interactions (tDDI). It is the transporter
most frequently tested for tDDIs both in vitro and in the clinic.
Objective: Understanding the limitations of various in vitro and in vivo models, therefore, is crucial. In this review
we cover regulatory aspects of ABCB1 mediated drug transport as well as inhibition and the available models and methods. We also discuss
protein structure and mechanistic aspects of transport as ABCB1 displays complex kinetics that involves multiple binding sites, potentiation
of transport and probe-dependent IC50 values.
Results: Permeability of drugs both passive and mediated by transporters is also a covariate that modulates apparent kinetic values. Levels
of expression as well as lipid composition of the expression system used in in vitro studies have also been acknowledged as determinates
of transporter activity. ABCB1-mediated clinical tDDIs are often complex as multiple transporters as well as metabolic enzymes
may play a role. This complexity often masks the role of ABCB1 in tDDIs.
Conclusion: It is expected that utilization of in vitro data will further increase with the refinement of simulations. It is also anticipated
that transporter humanized preclinical models have a significant impact and utility.