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1. Drug Metab Dispos. 2012 Feb 16. [Epub ahead of print]

Stereoselective Interaction of Pantoprazole with ABCG2: I. Drug Accumulation in
Rat Milk.

Wang L, McNamara PJ.

University of Kentucky.

Active transport of drug into milk is a major concern in breastfeeding. Abcg2
plays a critical role in drug transfer into rat milk which is consistent with
evidence in humans. Although it is estimated that about half of all therapeutic
agents are chiral, there have been few reports of stereoselective interactions
with ABCG2. The purpose of this study was to investigate the interaction of
pantoprazole (PAN) isomers with Abcg2 in in vitro and in vivo experiments.
Pantoprazole isomer flux was characterized using Abcg2 -MDCKII cells in
Transwells. In a crossover design, lactating Sprague-Dawley lactating rats were
used to study PAN accumulation in milk after an i.v. infusion of pantoprazole
mixture after Abcg2 inhibitor (GF120918). Samples were analyzed by HPLC/LC-MS.
The results indicated that pantoprazole isomers were transported in an identical
fashion in vector-MDCKII cell lines, whereas a significant difference in flux was
observed in Abcg2-MDCKII cell line. The administration of GF120918 slightly
increased the concentration of both isomers in serum, but no statistical
difference was observed. However, the systemic clearance of (+) PAN (0.57±0.1)
was larger than (-) PAN (0.44±0.12) (p<0.01). Milk to serum ratio of (-) PAN
(1.36±0.20) was 2.5 fold greater than that of (+) PAN (0.54±0.09) (p<0.01).
Administration of GF120918 decreased M/S of (-) PAN to 0.50±0.08 (p<0.001) and
(+) PAN to 0.38±0.07 (p>0.05). In conclusion, Abcg2 interacts stereoselectively
with PAN isomers which is responsible for their differential accumulation in
milk. Stereoselective transport of ABCG2 may have broader consequences in drug

PMID: 22344699 [PubMed - as supplied by publisher]