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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1981-04

AUTHORS

T. Wagner, D. Heydrich, T. Jork, G. Voelcker, H. J. Hohorst

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. More... »

PAGES

95-104

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf00405906

DOI

http://dx.doi.org/10.1007/bf00405906

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030287881

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/7240346


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