Secretory transport of irinotecan metabolite SN-38 across isolated intestinal tissue.
OBJECTIVE
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.
Itagaki
Shirou
S
Department of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan.
Sumi
Yoshinobu
Y
Shimamoto
Soji
S
Itoh
Tatsuya
T
Hirano
Takeshi
T
Takemoto
Isao
I
Iseki
Ken
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000378:metabolism*; D004396:Coloring Agents / Q000494:pharmacology; D007421:Intestine, Small / Q000378:metabolism*; D000077146:Irinotecan; D008297:Male; D008942:Mitoxantrone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013448:Sulfobromophthalein / Q000494:pharmacology
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D013448:Sulfobromophthalein; D000077146:Irinotecan; D008942:Mitoxantrone; D002166:Camptothecin