title: A new strategy to rapidly evaluate kinetics of glucuronide efflux by breast cancer resistance protein (BCRP/ABCG2).
abstract: OBJECTIVE
  The efflux transporter breast cancer resistance protein (BCRP/ABCG2) plays an important role in excretion of anionic drugs and metabolites including glucuronides in humans.
  
  
  METHODS
  In this article, our recently published cell model (i.e., HeLa cells over-expressing UGT1A9 (HeLa1A9)) is used to determine the kinetic parameters of BCRP-mediated transport of glucuronides.
  
  
  RESULTS
  After incubation of the aglycone with the cells, a steady-state (i.e., zero-order or near zero-order) excretion of its glucuronide is rapidly achieved and then maintained. Kinetic profiling with different (intracellular) glucuronide concentrations and their corresponding excretion rates is enabled by varying the concentration of the aglycone, which allows for the determination of kinetic parameters responsible for BCRP-mediated efflux of glucuronides. This approach was validated theoretically using a cellular pharmacokinetic model incorporating various enzymatic and transporter-mediated kinetic processes. It was also validated experimentally in that kinetic parameters of efflux of glucuronides of 6-hydroxyflavone and 4-methylumberiferone in the HeLa1A9 cell model were shown to be consistent with those derived with BCRP-overexpressing membrane vesicles.
  
  
  CONCLUSIONS
  This study provides a new strategy for rapidly evaluating the kinetics of glucuronide efflux by BCRP.
authors: Department of Pharmacological & Pharmaceutical Sciences, College of Pharmacy, University of Houston, 1441 Moursund Street, Houston, Texas 77030, USA.
authors: Baojian
authors: B
authors: Wu
authors: Wen
authors: W
authors: Jiang
authors: Taijun
authors: T
authors: Yin
authors: Song
authors: S
authors: Gao
authors: Ming
authors: M
authors: Hu
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D001692:Biological Transport; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005419:Flavonoids / Q000493:pharmacokinetics; D020719:Glucuronides / Q000493:pharmacokinetics*; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D005419:Flavonoids; D020719:Glucuronides; D009363:Neoplasm Proteins; C529356:6-hydroxyflavone