Abstract
The pharmacokinetics of high-dose cytosine arabinoside (ara-C) were studied in 18 patients with acute leukemia and high-grade non-Hodgkin's lymphoma. The plasma concentrations of ara-C increased in proportion to the dose over a range of 1-3 g/m2. The initial and terminal half-lives were not influenced by the dose or schedule of administration and no accumulation of ara-C occurred with repeated dosage in the same patients. These data suggest that cytidine deaminase is not saturated within this dose range. The cerebrospinal fluid (CSF) concentrations of ara-C also rose linearly with the increase in dose and varied from 347 ng/mL (1 g/m2) to 1,070 ng/mL (3 g/m2). The mean CSF concentrations of ara-C following high-dose infusions over three hours were 6%-22% of simultaneous plasma concentrations. Three hours after completion of the intravenous infusion the CSF concentrations were greater than the corresponding plasma concentrations owing to the long half-life of ara-C in CSF compared to that in plasma. These data demonstrate that therapy with intravenous high-dose ara-C given twice daily provides continuous levels in the CSF at concentrations that are likely to be of value in the treatment of central nervous system leukemia.
Published Version
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