pH-Dependent passive and active transport of acidic drugs across Caco-2 cell monolayers
2005 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 25, no 2-3, 211-220 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 25, no 2-3, 211-220 p.
Biological Transport; Active, Caco-2 Cells, Cell Membrane/*metabolism, Cell Membrane Permeability/*drug effects, Humans, Hydrogen-Ion Concentration, Indomethacin/*pharmacokinetics, Research Support; Non-U.S. Gov't, Salicylic Acid/*pharmacokinetics
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-93110DOI: 10.1016/j.ejps.2005.02.009PubMedID: 15911216OAI: oai:DiVA.org:uu-93110DiVA: diva2:166488