Altered pharmacokinetics and metabolism of CPT-11 in liver dysfunction: A need for guidelines

C. J. Van Groeningen, W. J F Van Der Vijgh, J. J. Baars, H. Stieltjes, K. Huibregtse, H. M. Pinedo

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Metabolic conversion of CPT-11 is a major route of elimination of this new topoisomerase 1 inhibitor. Presently, recommendations for dose adjustments of CPT-11 in patients with liver dysfunction are lacking. We describe the case of a patient with metastatic colon cancer with liver dysfunction treated with CPT-11 at two different dose levels (100 mg/m2 and 30 mg/m2, single dose, administered as a 90-min i.v. infusion). The lactones and carboxylates of CPT-11 and SN-38 were determined by high-performance liquid chromatography. SN-38 glucuronide was determined after deglucuronidation. The procedures allowed intrapatient comparison of pharmacokinetics and metabolism of the drug. Severe side effects were encountered, which could be explained by the reduced clearance of CPT-11 and its metabolites. These included neutropenic fever with culture-proven septicemia, thrombocytopenia, somnolence, diarrhea, and signs and symptoms of transient hepatic failure. Our findings offer important data for the further development of guidelines for dose reduction of CPT-11 in patients with liver dysfunction.

Original languageEnglish (US)
Pages (from-to)1342-1346
Number of pages5
JournalClinical Cancer Research
Issue number4
StatePublished - Apr 2000
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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