title: Secretory transport of irinotecan metabolite SN-38 across isolated intestinal tissue.
abstract: 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.
authors.affiliation: 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.
authors.forename: Shirou
authors.initials: S
authors.lastname: Itagaki
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Sumi
authors.forename: Soji
authors.initials: S
authors.lastname: Shimamoto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Itoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirano
authors.forename: Isao
authors.initials: I
authors.lastname: Takemoto
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D013448:Sulfobromophthalein; D000077146:Irinotecan; D008942:Mitoxantrone; D002166:Camptothecin