The in vivo activation of cyclophosphamide (Endoxan) to cytostatic and alkylating metabolites has been studied. Endoxan is metabolized to the weak anion by microsomal dealkylation in the rat's liver; this product is the first alkylating metabolite. About 80% of the alkylating activity of the serum, occurring 30 min after injection of Endoxan is presented by this primary alkylating metabolite. Nor-N-mustard and N-2-chloroethyl-aziridine were found only in traces. Although some activation was detected in the liver, the lungs and to a minor extent the kidneys, this phenomenon has not been detected i n the screened experimental rat tumors. The authors conclude that the greater specificity of Endoxan as compared to other cytostatic agents of the N-mustard group may be due to some specific permeation properties of the primary alkylating metabolite of Endoxan rather than to a possible specific mechanism of action of this compound within tumor cells.
NDOXAN* SHOWS A SIGNIFICANTLY GREATER gen mustard series.l, 2, 5 This can be quantita-E selectivity against many kinds of tumor tively assessed in vivo by the higher therapeucells than other cytostatic agents of the nitro-tic index of Endoxan in many experimental tumors (Table ). T h e wider margin of safety k'roni the Pharmacological Division, ASTA-Werke of the drug is mainly due to its reduced gen-AG.,