Effect of bile acids on the uptake of irinotecan and its active metabolite, SN-38, by intestinal cells.
The intestinal transport of irinotecan (CPT-11) and its active metabolite, SN-38, has been previously reported (K. Kobayashi et al., Int. J. Cancer, 83 (1999) 491-496). In the present study, the effect of the two major primary bile acids, cholic acid (CA) and taurocholic acid (TCA), on the uptake of CPT-11 and SN-38 by hamster intestinal epithelial cells was investigated. These two bile acids at concentrations up to 200 microM did not directly alter the cellular uptake of CPT-11 and SN-38. However, under physiologically acidic intestinal pH conditions, micelle formation induced by 20 mM TCA significantly reduced the cellular uptake of CPT-11 and SN-38 by 60% and 80%, respectively.
Kobayashi
K
K
Department of Medicine, George Washington University Medical Center, Wahington, DC 20037, USA.
Ceryak
S
S
Matsuzaki
Y
Y
Kudoh
S
S
Bouscarel
B
B
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D019826:Cholic Acid / Q000494:pharmacology; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D000077146:Irinotecan; D008647:Mesocricetus; D008823:Micelles; D013656:Taurocholic Acid / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D001647:Bile Acids and Salts; D004791:Enzyme Inhibitors; D008823:Micelles; D059004:Topoisomerase I Inhibitors; D013656:Taurocholic Acid; D000077146:Irinotecan; D019826:Cholic Acid; D002166:Camptothecin