Biliary excretion of irinotecan and its metabolites

J Pharm Pharm Sci. 2004 Jan 23;7(1):13-8.


Purpose: The aim of this study was to investigate the excretion of irinotecan hydrochloride (CPT-11) and its metabolites into the gastrointestinal lumen via the biliary route after intravenous administration of lactone and carboxylate forms of CPT-11.

Methods: Biliary excretions of CPT-11 and its metabolites, SN-38 and SN-38-glucuronide, were investigated by an in vivo administration study using rats. The biliary excretion profiles for both the lactone and carboxylate forms of CPT-11 and its metabolites were determined.

Results: After the i.v. injection of the lactone form of CPT-11, the cumulative biliary excretion of SN-38-glucuronide was much greater than that of CPT-11 and SN-38, and biliary excretion of SN-38 was less than that of CPT-11. Further, CPT-11 and SN-38 were mainly excreted into bile as carboxylate forms. After the administration of the CPT-11 carboxylate form, biliary excretion of SN-38-glucuronide was significantly smaller than that after the administration of CPT-11 lactone form. On the other hand, biliary excretion of CPT-11 and SN-38 was greater after dosing with the CPT-11 carboxylate form than that after the CPT-11 lactone form.

Conclusions: The results suggest that the rate of conversion of lactone to carboxylate forms of CPT-11 and its metabolites plays a major role in the biliary excretion of these compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Biliary Tract / metabolism*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / metabolism
  • Camptothecin / pharmacokinetics*
  • Carboxylic Acids / chemistry
  • Glucuronides / pharmacokinetics*
  • Irinotecan
  • Lactones / chemistry
  • Male
  • Rats
  • Rats, Wistar


  • 7-ethyl-10-hydroxycamptothecin glucuronide
  • Antineoplastic Agents, Phytogenic
  • Carboxylic Acids
  • Glucuronides
  • Lactones
  • Irinotecan
  • Camptothecin