Über Blutspiegel und Urin-Ausscheidung von aktiviertem Cyclophosphamid und seinen Deaktivierungsprodukten beim Menschen View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1980-01

AUTHORS

Th. Wagner, D. Heydrich, G. Voelcker, H. J. Hohorst

ABSTRACT

Blood levels and urinary excretion of cyclophosphamide and its metabolites were determined in cancer patients receiving cyclophosphamide. Activated cyclophosphamide (4-hydroxycyclophosphamide aldophosphamide) was assayed by TLC after derivatisation to stable 4-(S-benzyl)-sulfido-cyclophosphamide. Twenty minutes after injection of 10(20) mg/kg cyclophosphamide mean peak levels of activated cyclophosphamide were found to be 1.4(2.6) nmol/ml. The rate constant for biotransformation (=activation) of cyclophosphamide in man (km = 0.132 h-1) was only 1/50 of the value found in the mouse whereas the elimination rate constant of activated cyclophosphamide (ke[M] approximately 6.78 h-1) was much higher equalling that of laboratory animals. 4-ketocyclophosphamide, carboxyphosphamide, and phosphoramidemustard reached their peak levels between 4 and 6 h after cyclophosphamide injection. Increasing quantities of cyclophosphamide metabolites were bound to plasma proteins reaching a constant level after 24 h lasted for several days. Fifty per cent of those metabolites were reversibly bound to plasma proteins. Within 24 h, the cumulative excretion of cyclophosphamide and its metabolites amounted to 50% of the dose applied. The main metabolites excreted were phosphoramide-mustard and carboxyphosphamide whereas only 2% consisted of activated cyclophosphamide. The significance of the different pharmacokinetics of cyclophosphamide in laboratory animals and man for the therapeutic index is discussed. More... »

PAGES

79-92

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf00412899

DOI

http://dx.doi.org/10.1007/bf00412899

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000700150

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/7358774


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