Cytosine arabinoside cerebrospinal fluid kinetics.
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.
D000293:Adolescent; D001086:Arabinofuranosyluracil / Q000134:cerebrospinal fluid / Q000378:metabolism; D002648:Child; D003561:Cytarabine / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007276:Injections, Intraventricular; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008657:Metabolic Clearance Rate
D003561:Cytarabine; D001086:Arabinofuranosyluracil