Cyclophosphamide plasma and cerebrospinal fluid kinetics with and without dimethyl sulfoxide

Ten patients with brain tumors and indwelling ventricular reservoirs were pretreated with 5% to 10% dimethyl sulfoxide (DMSO) (intravenous, oral, or both) and were then treated with 1.0 to 1.25 gm/m² cyclophosphamide (CYC). All patients were also on anticonvulsants and dexamethasone. CYC and alkylating activity (alk act) in plasma and concomitant ventricular cerebrospinal fluid (CSF) were measured by gas chromatography and p-nitrobenzyl pyridine assay. CYC entered the CSF without difficulty and was lost from CSF more slowly than from plasma. Alk act did not enter CSF as well as did CYC. DMSO did not alter any measured aspect of CYC or alk act disposition. Specifically, it did not alter the CYC plasma half-life (t 1 2), CSF t 1 2, peak CSF: peak plasma CYC concentration ratio, or the urinary excretion of CYC. DMSO did not alter the plasma t 1 2 or urinary excretion of alk act or the peak CSF: peak plasma concentration ratio of alk act. Our data show reduced plasma t 1 2 of CYC and increased plasma and urinary alk act. This may reflect the effect of long-term therapy with anticonvulsants or steroids.