Interactions of Oral Molecular Excipients with Breast Cancer Resistance Protein, BCRP

Mol Pharm. 2020 Mar 2;17(3):748-756. doi: 10.1021/acs.molpharmaceut.9b00658. Epub 2020 Feb 10.


Mechanistic-understanding-based selection of excipients may improve formulation development strategies for generic drug products and potentially accelerate their approval. Our study aimed at investigating the effects of molecular excipients present in orally administered FDA-approved drug products on the intestinal efflux transporter, BCRP (ABCG2), which plays a critical role in drug absorption with potential implications on drug safety and efficacy. We determined the interactions of 136 oral molecular excipients with BCRP in isolated membrane vesicles and identified 26 excipients as BCRP inhibitors with IC50 values less than 5 μM using 3H-cholecystokinin octapeptide (3H-CCK8). These BCRP inhibitors belonged to three functional categories of excipients: dyes, surfactants, and flavoring agents. Compared with noninhibitors, BCRP inhibitors had significantly higher molecular weights and SLogP values. The inhibitory effects of excipients identified in membrane vesicles were also evaluated in BCRP-overexpressing HEK293 cells at similar concentrations. Only 1 of the 26 inhibitors of BCRP identified in vesicles inhibited BCRP-mediated 3H-oxypurinol uptake by more than 50%, consistent with the notion that BCRP inhibition depends on transmembrane or intracellular availability of the inhibitors. Collectively, the results of this study provide new information on excipient selection during the development of drug products with active pharmaceutical ingredients that are BCRP substrates.

Keywords: BCRP; drug−excipient interaction; excipient.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism*
  • Administration, Oral
  • Coloring Agents / chemistry
  • Coloring Agents / metabolism*
  • Coloring Agents / pharmacology
  • Drug Compounding / methods
  • Drug Evaluation, Preclinical / methods
  • Excipients / chemistry
  • Excipients / metabolism*
  • Excipients / pharmacology
  • Female
  • Flavoring Agents / chemistry
  • Flavoring Agents / metabolism*
  • Flavoring Agents / pharmacology
  • HEK293 Cells
  • Humans
  • Inhibitory Concentration 50
  • Intestinal Absorption / drug effects
  • Molecular Weight
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Signal Transduction / genetics
  • Surface-Active Agents / chemistry
  • Surface-Active Agents / metabolism*
  • Surface-Active Agents / pharmacology
  • Transfection


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Coloring Agents
  • Excipients
  • Flavoring Agents
  • Neoplasm Proteins
  • Surface-Active Agents