bcrp - publications

Predict more bcrp - ligand interactions now!

1. Drug Metab Dispos. 2012 Feb 21. [Epub ahead of print]

Stereoselective Interaction of Pantoprazole with ABCG2: II. In Vitro Flux

Wang L, Leggas M, Empey PE, McNamara PJ.

1 University of Kentucky;

(-) Pantoprazole (PAN) accumulated in rat milk stereoselectively and this
accumulation was attributed to rAbcg2. In contrast, flux experiments at 25 μM
showed that (+) PAN was preferentially transported by rAbcg2. The purpose of the
current study was to comprehensively evaluate the transport of PAN isomers in
empty-MDCKII and MDCKII cells expressing the human/rat (ABCG2/rAbcg2) isoforms at
concentrations ranging from 3 to 200μM. The apical to basolateral (A to B) and
basolateral to apical (B to A) directional flux and the asymmetry efflux ratios
(ERα) were virtually identical for both isomers in empty(mock transfected)-MDCKII
monolayers, but were concentration dependent for both isomers in ABCG2
(human/rat)-MDCKII. Kinetic analysis using predicted cellular concentrations
showed that (-) PAN had an 8-fold lower K(M) compared to (+) PAN for both rAbcg2
(0.25 vs 1.85 μM) and ABCG2 (0.6 vs 5.32 μM). (+) PAN had a 3-fold higher T(Max)
compared to the (-) PAN for both rAbcg2 (7.86 vs 2.49 nmol/hr*cm(2)) and ABCG2
(10.2 vs 3.29 nmol/hr*cm(2)). Effective ABCG2 surface area permeability of
(PS(AE,Eff)) of (-) PAN was 9,920 and 5,480 (μL/hr)/cm(2) for rAbcg2 and ABCG2,
respectively compared to the (+) PAN isomer (4,250 and 1,920 μL/hr*cm(2),
respectively). These results indicate a stereoselective interaction of PAN with
similar kinetic parameters for both human and rat ABCG2. (-) PAN is a better
substrate than (+) PAN for ABCG2/rAbcg2 and provide a rationale for the
preferential accumulation of (-) PAN into rat milk.

PMID: 22355035 [PubMed - as supplied by publisher]