Cytosine arabinoside cerebrospinal fluid kinetics

Clin Pharmacol Ther. 1984 Jun;35(6):826-30. doi: 10.1038/clpt.1984.120.


To better characterize the disposition of cytosine arabinoside (Ara-C) in cerebrospinal fluid (CSF), its kinetics were studied in seven patients with meningeal leukemia in complete remission. After intraventricular injection of 30 mg Ara-C, CSF and plasma samples were obtained over a 24-hr period. Ara-C levels were measured by a reverse-phase HPLC assay (with a sensitivity of 0.5 microM in CSF and 1.0 microM in plasma) that readily separated Ara-C from its major metabolite uracil arabinoside (Ara-U). Elimination of Ara-C from CSF followed a biphasic pattern, with an initial t1/2 of 1 hr and a terminal t1/2 of 3.4 hr. Ara-C clearance from CSF was 0.42 ml/min, suggesting that drug elimination was primarily by CSF bulk flow. The ratio of the AUC of Ara-U to the AUC of Ara-C was 0.08, indicating only minor metabolism of Ara-C to Ara-U in CSF, in contrast to that after systemic Ara-C. Despite initial CSF Ara-C concentrations exceeding 2 mM, Ara-C was not detectable in plasma in any patient. Intraventricular Ara-C results in very high levels in CSF, but systemic tissues are relatively spared from exposure to Ara-C.

MeSH terms

  • Adolescent
  • Arabinofuranosyluracil / cerebrospinal fluid
  • Arabinofuranosyluracil / metabolism
  • Child
  • Cytarabine / administration & dosage
  • Cytarabine / blood
  • Cytarabine / cerebrospinal fluid*
  • Female
  • Humans
  • Injections, Intraventricular
  • Kinetics
  • Leukemia, Lymphoid / drug therapy
  • Leukemia, Lymphoid / metabolism
  • Male
  • Meningeal Neoplasms / drug therapy
  • Meningeal Neoplasms / metabolism
  • Metabolic Clearance Rate


  • Cytarabine
  • Arabinofuranosyluracil