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In vitro evaluation of potential transporter‐mediated drug interactions of evogliptin
Author(s) -
Lee Dae Y.,
Chae Hye W.,
Shim Hyun J.
Publication year - 2017
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2083
Subject(s) - transporter , chemistry , in vitro , efflux , pharmacology , biochemistry , biology , gene
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.