Cytosine arabinoside cerebrospinal fluid kinetics

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Abstract
To better characterize the disposition of cytosine arabinoside (Ara-C) in CSF, its kinetics were studied in 7 patients with meningeal leukemia in complete remission. After intraventricular injection of 30 mg Ara-C, CSF and plasma samples were obtained over a 24-h period. Ara-C levels were measured by a reverse-phase HPLC [high-performance liquid chromatography] assay (with a sensitivity of 0.5 .mu.M in CSF and 1.0 .mu.M 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 [half-life] of 1 h and a terminal t1/12 of 3.4 h. 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. Depspite 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.

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