BLOOD-LEVELS OF ALKYLATING METABOLITES OF CYCLOPHOSPHAMIDE IN THE MOUSE AFTER IV OR ORAL-ADMINISTRATION

  • 1 January 1984
    • journal article
    • research article
    • Vol. 68  (5) , 765-770
Abstract
Blood levels of cyclophosphamide (CPA) and its alkylating metabolites in mice were determined after i.v. or oral administration of a 200-mg/kg dose of radiolabeled CPA. Individual metabolites (4-hyroxy-CPA, 4-keto-CPA, alcophosphamide, dechloroethyl-CPA, carboxyphosphamide and phosphoramide mustard) were isolated from blood by solvent extraction and by TLC. Area-under-the-blood-decay-curve (AUC) values were determined for CPA and its alkylating metabolites to provide a basis for comparison of systemic exposure by i.v. or oral treatment. The total AUC values for alkylating metabolites of CPA was observed to be greater after i.v. administration, and AUC values for each of the individual metabolites were greater after i.v. treatment, except for the minor metabolite alcophosphamide. These methods were applied to 1 patient to date and will be used in future studies with other patients to determine relative AUC values for the oncolytic CPA metabolites 4-hydroxy-CPA and phosphoramide mustard.