A Correlation Between Cyclophosphamide Induced Leukopenia in Mice and the Presence of Alkylating Metabolites

Cyclophosphamide (75, 100, and 300 mg/kg, ip) produced a significant decrease in total white blood cell counts between 1 and 5 days after drug treatment. There was a significant dose-related effect 3 days after treatment. Phenobarbital pretreatment significantly increased both the in vitro production of alkylating metabolites and cyclophosphamide-induced leukopenia 2 days after treatment. SKF 525-A pretreatment significantly reduced both the in vitro formation of alkylating metabolites and the drug-induced leukopenia at 4 and 6 days after treatment. These observations indicate that alkylating metabolites of cyclophosphamide are responsible for the dose-related leukopenic effect of this antineoplastic agent.