pH-Dependent passive and active transport of acidic drugs across Caco-2 cell monolayers

Eur J Pharm Sci. 2005 Jun;25(2-3):211-20. doi: 10.1016/j.ejps.2005.02.009. Epub 2005 Mar 23.


The aim of this study was to investigate pH-dependent passive and active transport of acidic drugs across Caco-2 cells. Therefore, the bidirectional pH-dependent transport of two acidic drugs, indomethacin and salicylic acid, across Caco-2 cells was studied in the physiological pH range of the gastrointestinal tract. The transport of both drugs decreased with increased pH, as expected from the pH-partition hypothesis. Net absorption occurred when the basolateral pH exceeded the apical pH. Concentration dependence and transporter inhibition studies indicated passive transport for indomethacin and a mixture of pH-dependent passive and active influx for salicylic acid. Unexpectedly, active and passive drug transport results were indistinguishable in temperature dependency studies. The transport of salicylic acid (apical pH 5.0; basolateral pH 7.4) was partly blocked by inhibitors of the proton-dependent transporters MCT1 (SLC16A1) and OATP-B (SLC21A9, SLCO2B1). This study shows that the asymmetry in bidirectional transport of acidic drugs is affected by both passive and active components in the presence of pH gradients across Caco-2 cells. Thus, combined studies of concentration-dependency and transport-inhibition are preferred when acidic drug transport is studied in a pH gradient. The findings of this in vitro study can be extrapolated to in vivo situations involving an acidic microclimate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport, Active
  • Caco-2 Cells
  • Cell Membrane / metabolism*
  • Cell Membrane Permeability / drug effects*
  • Humans
  • Hydrogen-Ion Concentration
  • Indomethacin / pharmacokinetics*
  • Salicylic Acid / pharmacokinetics*


  • Salicylic Acid
  • Indomethacin