Uptake of irinotecan metabolite SN-38 by the human intestinal cell line Caco-2.
OBJECTIVE
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.
Itoh
Tatsuya
T
Department of Pharmacy, Sapporo Social Insurance General Hospital, Chuo 2-jo, 6-chome, Atsubetsu-ku, Sapporo 004-8618, Japan.
Itagaki
Shirou
S
Sumi
Yoshinobu
Y
Hirano
Takeshi
T
Takemoto
Isao
I
Iseki
Ken
K
D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004396:Coloring Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D000077146:Irinotecan; D013448:Sulfobromophthalein / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D013448:Sulfobromophthalein; C038044:baicalin; D000077146:Irinotecan; D002166:Camptothecin