Comparative study on human pharmacokinetics of activated ifosfamide and cyclophosphamide by a modified fluorometric test

J Cancer Res Clin Oncol. 1981;100(1):95-104. doi: 10.1007/BF00405906.

Abstract

The activated metabolites of ifosfamide and cyclophosphamide (4-hydroxy-ifosfamide and 4-hydroxy-cyclophosphamide) were analysed fluorometrically by condensation of liberated acrolein with m-aminophenol yielding 7-hydroxyguinoline. Interfering fluorescence of blood and urine was eliminated by extraction with dichlormethane and determination of blanks in which the liberated acrolein reacted with hydrazine to non-fluorescent pyrazoline. The modified test proved effective in identifying low levels of activated metabolites in man. After i.v. injection of 20 mg/kg cyclophosphamide or ifosfamide peak levels of activated cyclophosphamide (4.7 nmol/ml) and the area under the curve (c.t = 16.7 nmol.ml/h) showed mean values three times higher than those found for activated ifosfamide. One per cent of the applied dosis of cyclophosphamide vs. 0.3% of ifosfamide was excreted as activated metabolites. Due to the high stability of activated cyclophosphamide and ifosfamide in urine a low liberation rate of acrolein was found, the concentration of which in urine was below 0.5 nmol/ml. Acrolein, which was directly liberated from activated cyclophosphamide or ifosfamide, does not seem to play an important role in the urotoxicity of these cytostatics.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrolein / metabolism
  • Biotransformation
  • Cyclophosphamide / analogs & derivatives*
  • Cyclophosphamide / metabolism*
  • Female
  • Humans
  • Ifosfamide / metabolism*
  • Kinetics
  • Male
  • Middle Aged
  • Spectrometry, Fluorescence

Substances

  • Acrolein
  • Cyclophosphamide
  • Ifosfamide