Characterization of loxoprofen transport in Caco‐2 cells: the involvement of a proton‐dependent transport system in the intestinal transport of loxoprofen

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 mm , 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 [¹⁴C] 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 [¹⁴C] 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.