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

Abstract

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 : 4.8 mm, V : 142 nmol/mg protein/30 s, and K : 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 [ 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 [ 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.

Pharmacological Inhibition of MCT4 Reduces 4-Hydroxytamoxifen Sensitivity by Increasing HIF-1α Protein Expression in ER-Positive MCF-7 Breast Cancer Cells

“…Western Blotting Western blotting was performed as described in our previous study, with minor modifications. 17) The following antibodies were used for Western blotting: MCT1 (sc-365501, diluted 1 : 250; Santa Cruz Biotechnology, Dallas, TX, U.S.A.), MCT4 (22787-1-AP, diluted 1 : 1000; ProteinTech Group, Inc., Chicago, IL, U.S.A.), hypoxia-inducible factor 1α (HIF-1α) (sc-10790, diluted 1 : 200; Santa Cruz Biotechnology), β-actin (MAB1501, diluted 1 : 1000; Millipore, Bedford, MA, U.S.A.), anti-mouse secondary antibody (1070-05, diluted 1 : 4000; Southern Biotech, Birmingham, AL, U.S.A.), and anti-rabbit secondary antibody (sc-2357, diluted 1 : 4000; Santa Cruz Biotechnology).…”

Synthesis of α-cyanato-α′-carbonyl sulfoxonium ylides in water

“…In Scheme 4a, we demonstrate the application potential of our reaction by testing it on pharmacologically active drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs) were widely used, [44][45][46][47][48] and we successfully applied our reaction to substrates derived from naproxen, 46,48 loxoprofen, 44 and oxaprozin, 45 yielding the desired products 29b-31b in 60% to 72% yields. Furthermore, substrate 32b derived from probenecid which was widely used as an antigout drug, 49 underwent excel- a Reaction conditions: 1a (0.2 mmol), TsCN(0.4 mmol, 2 eq.…”