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, 8 3 (1999) 491-496). In the present study, the effect of the two major primar y 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 muM did not directly alter the cellular uptake of CPT-11 and SN-38. However, under physiologically ac idic intestinal pH conditions, micelle formation induced by 20 mM TCA signi ficantly reduced the cellular uptake of CPT-II and SN-38 by 60% and 80%, re spectively. (C) 2001 Elsevier Science B.V. All rights reserved.