Uptake of irinotecan metabolite SN-38 by the human intestinal cell line Caco-2

Cancer Chemother Pharmacol. 2005 May;55(5):420-4. doi: 10.1007/s00280-004-0937-4. Epub 2004 Nov 23.

Abstract

Purpose: The aim of this study was to investigate the transport mechanisms of transporters that contribute to the intestinal uptake of 7-ethyl-10-hydroxycamptothecin (SN-38).

Methods: Human intestinal epithelial Caco-2 cells were used to investigate the mechanistic basis of transepithelial uptake of SN-38. We investigated the characteristics of SN-38 uptake into Caco-2 cells. The effects of baicalin and sulfobromophthalein (BSP) on the uptake of SN-38 by Caco-2 cells were examined.

Results: Uptake of SN-38 was significantly reduced at 4 degrees C. Baicalin inhibited the uptake of SN-38 in a concentration-dependent manner. BSP significantly reduced the uptake of SN-38. However, probenecid, pravastatin and grepafloxacin did not affect the uptake of SN-38.

Conclusions: The results suggest that a specific transport system mediates the uptake of SN-38 across the apical membrane in Caco-2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Biological Transport / drug effects
  • Caco-2 Cells
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacokinetics*
  • Coloring Agents / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Flavonoids / pharmacology*
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects
  • Irinotecan
  • Sulfobromophthalein / pharmacology*
  • Tumor Cells, Cultured / drug effects*
  • Tumor Cells, Cultured / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Coloring Agents
  • Enzyme Inhibitors
  • Flavonoids
  • Sulfobromophthalein
  • baicalin
  • Irinotecan
  • Camptothecin