Role of basolateral efflux transporter @entity36620 in the intestinal absorption of the antiviral drug XXXX .

@entity24488 @entity11092 @entity24810 @entity3352 @entity36620
@entity24810 is a diester prodrug of the antiviral drug @entity24488 , with much greater oral bioavailability than @entity24488 . Evidence shows that the prodrug is metabolized to @entity24488 in the enterocytes during intestinal absorption. However, it is unknown how the highly charged and hydrophilic @entity24488 crosses the basolateral membrane in the intestine. This study determines the role of specific basolateral transporter(s) in the egress of @entity24488 across the basolateral membrane when formed from @entity24810 in Caco-2 cells, a model for intestinal epithelium. @entity36620 ( @entity36620 ) plays an important role in renal secretion of @entity24488 . Immunofluorescence images showed that @entity36620 is localized in the basolateral membrane of Caco-2 cells. This localization was further confirmed by Western blotting of the apical and basolateral membrane fractions that were isolated by a novel method involving biotinylation of respective membrane proteins and affinity enrichment. @entity36620 -knockdown Caco-2 cells were produced by stable transfection with @entity36620 -specific siRNA expression plasmid. These cells showed reduced @entity36620 protein expression and corresponding reduction in the basolateral egress of @entity24488 when @entity24810 was dosed on the apical side. A comparison of these data with the reduction in the basolateral egress of @entity24488 by the general @entity11092 inhibitor @entity3352 established that @entity36620 , among MRPs, plays a predominant role in the basolateral egress of @entity24488 in Caco-2 cells. The results highlight the importance of @entity36620 in oral absorption of @entity24810 , and suggest that significant drug-drug interactions can occur if an @entity36620 inhibitor is co-administered with @entity24810 .
