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Characterization of loxoprofen transport in Caco‐2 cells: the involvement of a proton‐dependent transport system in the intestinal transport of loxoprofen
Author(s) -
Narumi Katsuya,
Kobayashi Masaki,
Kondo Ayuko,
Furugen Ayako,
Yamada Takehiro,
Takahashi Natsuko,
Iseki Ken
Publication year - 2016
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.2026
Subject(s) - caco 2 , chemistry , lactic acid , transporter , propionate , multidrug resistance associated protein 2 , passive transport , biochemistry , pharmacology , atp binding cassette transporter , cell , bacteria , biology , membrane , genetics , gene
Loxoprofen, a propionate non‐steroidal anti‐inflammatory drug (NSAID), is used widely in East Asian countries. However, little is known about the transport mechanisms contributing to its intestinal absorption. The objectives of this study were to characterize the intestinal transport of loxoprofen using the human intestinal Caco‐2 cell model. The transport of loxoprofen was investigated in cellular uptake studies. The uptake of loxoprofen into Caco‐2 cells was pH‐ and concentration‐dependent, and was described by a Michaelis–Menten equation with passive diffusion ( K m : 4.8 m m , V max : 142 nmol/mg protein/30 s, and K d : 2.2 μl/mg protein/30 s). Moreover, the uptake of loxoprofen was inhibited by a typical monocarboxylate transporter (MCT) inhibitor as well as by various monocarboxylates. The uptake of [ 14 C] l ‐lactic acid, a typical MCT substrate, in Caco‐2 cells was saturable with relatively high affinity for MCT. Because loxoprofen inhibited the uptake of [ 14 C] l ‐lactic acid in a noncompetitive manner, it was unlikely that loxoprofen uptake was mediated by high‐affinity MCT(s). Our results suggest that transport of loxoprofen in Caco‐2 cells is, at least in part, mediated by a proton‐dependent transport system. Copyright © 2016 John Wiley & Sons, Ltd.