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

Invest New Drugs. 2005 Aug;23(4):317-30. doi: 10.1007/s10637-005-1440-4.

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 ([(14)C]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.

Publication types

  • Clinical Trial

MeSH terms

  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / urine
  • Biotransformation
  • Carbon Radioisotopes
  • Chemical Fractionation
  • Cholinesterase Inhibitors / pharmacokinetics*
  • Cholinesterase Inhibitors / urine
  • Chromatography, High Pressure Liquid
  • Glucuronides / metabolism
  • Humans
  • Infusions, Intravenous
  • Neoplasms / metabolism*
  • Neoplasms / urine
  • Spectrometry, Mass, Electrospray Ionization
  • Sulfonamides / pharmacokinetics*
  • Sulfonamides / urine
  • Urine / chemistry*

Substances

  • Antineoplastic Agents
  • Carbon Radioisotopes
  • Cholinesterase Inhibitors
  • Glucuronides
  • N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide
  • Sulfonamides