Ibuprofen is a non-competitive inhibitor of the peptide transporter hPEPT1 (SLC15A1): possible interactions between hPEPT1 substrates and ibuprofen.

06:00 EDT 24th August 2010 | BioPortfolio

Summary of "Ibuprofen is a non-competitive inhibitor of the peptide transporter hPEPT1 (SLC15A1): possible interactions between hPEPT1 substrates and ibuprofen."

Summary Background and purpose. Recently, we identified etodolac as a possible ligand for the human intestinal proton-couple peptide transporter (hPEPT1). This raised the possibility that other NSAIDs and especially ibuprofen could also interact with hPEPT1. Here, we have assessed the interactions of ibuprofen with hPEPT1. Experimental approach. The uptake of [(14)C]Gly-Sar, [(3)H]Ibuprofen and other radio-labelled compounds were investigated in MDCK/hPEPT1, MDCK/Mock, LLC-PK(1) or Caco-2 cells. The transepithelial transport of ibuprofen and hPEPT1 substrates was investigated in Caco-2 cell monolayers. Key results. Ibuprofen concentration-dependently inhibited hPEPT1-mediated uptake of Gly-Sar in MDCK/hPEPT1 cells (K(i) (app )= 0.4 mM) but uptake of ibuprofen in Caco-2 cells and MDCK/hPEPT1 cells was not inhibited by hPEPT1 substrates. The V(max) for Gly-Sar uptake was reduced from 522 pmol.min(-1).cm(-2 )to 181 pmol.min(-1).cm(-2) and 78 pmol.min(-1).cm(-2) in the presence of 0.5 mM and 1 mM ibuprofen, respectively. The interaction between ibuprofen and hPEPT1 was thus non-competitive. In LLC-PK1 cells, ibuprofen (1mM) did not influence the transporter-mediated uptake of glycine or alpha-methyl-D-glycopyranoside. In Caco-2 cell monolayers the absorptive transport of delta-aminolevulinic acid was reduced by 23 and 48 % by ibuprofen (1 and 10 mM), respectively. Likewise the transport of Gly-Sar was reduced by 23 % in the presence of ibuprofen (1 mM). Conclusions and implications. Ibuprofen is a non-competitive inhibitor of hPEPT1. As ibuprofen reduced the transepithelial transport of delta-aminolevulinic acid, drug-drug interactions between ibuprofen and hPEPT1 drug substrates at their site of absorption are possible if administered together.


Drug Transporters in ADME, Department of Pharmaceutics and Analytical Chemistry, The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.

Journal Details

This article was published in the following journal.

Name: British journal of pharmacology
ISSN: 1476-5381


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