Cerebrospinal Fluid Penetration of Active Metabolites of Cyclophosphamide and Ifosfamide in Rhesus Monkeys

The penetration of the active metabolites of cyclophosphamide (CP) and ifosfamide (IF) into cerebrospinal fluid (CSF) was determined in rhesus monkeys following an i.v. infusion of 1 gm/m2 of CP and IF. Active metabolites were measured using a high-performance liquid chromatography assay with fluorometric detection following derivatization with m-aminophenol. CSF to blood ratios of the active metabolites of CP and IF were found to be 0.17 and 0.13 following systemic dosing of CP and IF, respectively. The levels achieved in the CSF, however, were equivalent to levels known to be cytocidal to malignant cell lines derived from tumors which metastasize to the central nervous system. Only one animal demonstrated neurotoxicity with IF. CSF levels of active metabolite in this animal were similar to those observed in the other animals.