Secretory transport of irinotecan metabolite SN-38 across isolated intestinal tissue.

PURPOSE: The purpose of this study was to investigate the transport mechanisms of transporters that contribute to the intestinal efflux of 7-ethyl-10-hydroxycamptothecin (SN-38). METHODS: The intestinal transport of SN-38 was studied in rat intestinal tissue mounted in Ussing chambers. RESULTS: In the ileum, the level of transport from the serosal layer to the mucosal layer was significantly greater than that from the mucosal layer to the serosal layer, whereas a significant difference was not observed in the jejunum. This secretory transport required metabolic energy and was diminished by sulfobromophthalein. However, mitoxantrone, an inhibitor of breast cancer resistance protein (BCRP), did not affect the ileal secretion of SN-38. CONCLUSIONS: The results suggest that a specific transport system, which is distinct from BCRP, plays a major role in the secretion of SN-38 and that this secretory transport system predominantly exists in the ileum.

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

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.