Summary
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-hydroxychinolin. 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.
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Dedicated to Professor U. Ritter on his 60th birthday
With the support of the Bundesministerium für Forschung und Technologie, Bonn
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Wagner, T., Heydrich, D., Jork, T. et al. Comparative study on human pharmacokinetics of activated ifosfamide and cyclophosphamide by a modified fluorometric test. J Cancer Res Clin Oncol 100, 95–104 (1981). https://doi.org/10.1007/BF00405906
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DOI: https://doi.org/10.1007/BF00405906