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Investigational New Drugs

, Volume 23, Issue 4, pp 317–330 | Cite as

Human metabolism of [14C]indisulam following i.v. infusion in cancer patients

  • Jan-Hendrik Beumer
  • Michel J. X. Hillebrand
  • Dick Pluim
  • Hilde Rosing
  • Karen Foley
  • S. Murray Yule
  • Jan H. M. Schellens
  • Jos H. Beijnen
Article

Abstract

Indisulam is a new anticancer drug with a unique mechanism of action, arresting the cell cycle at the G1/S transition. The major excretory pathway of indisulam is via the urine, accounting for 63% of the radioactive dose ([14C]indisulam) administered in a human mass balance study. Radiochromatographic profiling of urine samples resulted in the detection of several radioactive peaks. The purpose of the present investigation was to elucidate the chemical structures of these observed indisulam metabolites. We collected fractions after chromatographic separation of the urine samples. These fractions were analysed using tandem mass spectrometry. We propose the chemical structure of 15 indisulam metabolites in urine. The metabolism of indisulam is very complex, consisting of oxidative dechlorination, hydroxylation, hydrolysis, acetylation, sulphation and glucuronidation. The clinical relevance of the observed indisulam metabolites needs further investigation.

Keywords

metabolism indisulam pharmacokinetics anticancer radiochromatography 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Jan-Hendrik Beumer
    • 1
  • Michel J. X. Hillebrand
    • 1
  • Dick Pluim
    • 2
  • Hilde Rosing
    • 1
  • Karen Foley
    • 3
  • S. Murray Yule
    • 3
  • Jan H. M. Schellens
    • 2
    • 4
  • Jos H. Beijnen
    • 1
    • 4
  1. 1.Department of Pharmacy & PharmacologySlotervaart Hospital/The Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Department of Medical OncologyAntoni van Leeuwenhoek Hospital/The Netherlands Cancer InstituteAmsterdamThe Netherlands
  3. 3.Eisai LimitedLondonUnited Kingdom
  4. 4.Department of Biomedical Analysis, Division of Drug Toxicology, Faculty of Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands

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