[Blood level and urinary excretion of activated cyclophosphamide and its deactivation products in man (author's transl)].
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.
D000368:Aged; D000818:Animals; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D010752:Phosphoramide Mustards / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D013045:Species Specificity
D001798:Blood Proteins; D010752:Phosphoramide Mustards; D003520:Cyclophosphamide; C000028:carboxyphosphamide; C008226:4-ketocyclophosphamide
Uber Blutspiegel und Urin-Ausscheidung von aktiviertem Cyclophosphamid und seinen Deaktivierungsprodukten beim Menschen.