Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11

Jpn J Cancer Res. 1993 Jun;84(6):697-702. doi: 10.1111/j.1349-7006.1993.tb02031.x.


Severe diarrhea occurred during daily intraperitoneal administration of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) at a dose of 50 mg/kg in athymic mouse. Serial determination of CPT-11 and 7-ethyl-10-hydroxycamptothecin (SN-38), with the use of an on-line solid extraction HPLC system, demonstrated that much higher levels of the compounds are retained in the intestine and the blood plasma after five consecutive daily injections than after a single injection. Histologic examination of the gastrointestinal tract showed hemorrhagic colitis on day 7 and later after five consecutive daily injections of CPT-11. The direct cause of diarrhea associated with CPT-11 administration is considered to be enterocolitis caused by high levels of SN-38 and/or CPT-11 retained for a long period in the intestine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / toxicity*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Camptothecin / metabolism
  • Camptothecin / toxicity
  • Chromatography, High Pressure Liquid
  • Diarrhea / etiology*
  • Enterocolitis / chemically induced
  • Injections, Intraperitoneal
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects*
  • Intestines / pathology
  • Irinotecan
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude


  • Antineoplastic Agents, Phytogenic
  • Irinotecan
  • Camptothecin