Intestinal efflux transporter

Intestinal efflux transporters are a specialized group of membrane-bound proteins located on the apical (luminal) surface of enterocytes in the small and large intestines (Source: Giacomini et al., Nature Reviews Drug Discovery, 2010). These transporters, primarily belonging to the ATP-binding cassette (ABC) superfamily, utilize ATP hydrolysis to actively pump a diverse range of substrates—including therapeutic drugs, dietary components, and environmental toxins—from the intracellular space back into the intestinal lumen (Source: NIH/NCBI StatPearls). The most clinically significant members are P-glycoprotein (P-gp/ABCB1), Breast Cancer Resistance Protein (BCRP/ABCG2), and Multidrug Resistance-associated Protein 2 (MRP2/ABCC2) (Source: FDA Guidance for Industry, 2020). By limiting the absorption of xenobiotics, these transporters serve as a critical biochemical barrier and are major determinants of the oral bioavailability and pharmacokinetic profile of many drugs (Source: UniProt P08183). They are also central to many drug-drug interactions, as the inhibition or induction of these transporters by one drug can significantly alter the plasma concentration and safety profile of a co-administered substrate (Source: PubMed PMID: 20125087). Consequently, evaluating the interaction of new drug candidates with these transporters is a regulatory requirement in drug development to ensure patient safety and therapeutic efficacy.

Other names

Intestinal efflux transportersApical efflux transportersIntestinal ABC transportersIntestinal xenobiotic pumpsP-glycoproteinBreast Cancer Resistance ProteinMultidrug Resistance-associated Protein 2

Inhibition of ATP-dependent efflux to increase systemic exposure of substrate drugs; induction of transporter expression to decrease substrate absorption.