%0 Journal Article
%T In vitro evaluation of potential transporter-mediated drug interactions of evogliptin.
%A Lee DY
%A Chae HW
%A Shim HJ
%J Biopharm Drug Dispos
%V 38
%N 6
%D Sep 2017
%M 28503751
%F 1.831
%R 10.1002/bdd.2083
%X To date, little is known about the transporter-mediated drug-drug interaction (DDI) potential of evogliptin, a novel DPP-4 inhibitor. The objective of this study was to evaluate the DDI potential of evogliptin using various in vitro assays in transporter-expressing cell lines. After incubating evogliptin with cells overexpressing OAT1, OAT3, OCT2, OATP1B1 and OATP1B3, there was no notable cellular accumulation of evogliptin (fold accumulation, 0.41-1.86). In bidirectional transport assays using a Caco-2 cell monolayer, a high efflux ratio (ER, 522) of evogliptin was observed, which was significantly decreased (97.96%) in the presence of a potent P-gp inhibitor. In assays using MDCKII-BCRP cell monolayers, by contrast, a low net ER (1.16-1.26) was found. In similar cellular uptake and bidirectional studies with probe substrates of P-gp, BCRP, OAT1, OAT3, OCT2, OATP1B1 and OATP1B3, the active transport of the substrates was not significantly suppressed by evogliptin. These results suggest that evogliptin may be a substrate of P-gp, but not a substrate of BCRP, OAT1B1, OAT1B3, OAT1, OAT3 or OCT2, and not an inhibitor of any of these transporters. Therefore, it could be concluded that evogliptin has some DDI potential involving P-gp, but it has low potential of DDI mediated by the other transporters.