Pharmacokinetic Studies of Intermediate- to High-Dose 1-β-D-Arabinofuranosylcytosine in Children With Acute Leukemia and Lymphoma

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Abstract
Pharmacokinetic studies of intermediate and high dose 1‐β‐d‐arabinofuranosylcytosine (araC) therapy were performed in 14 children with acute leukemia and four with non‐Hodgkin's lymphoma (NHL). AraC administration differed by method, dosage, and time of infusion to obtain the optimal tumorcidal concentration. The toxicity of these regimens was limited to transient severe nausea and vomiting, which were tolerable. Infusion time and dose are important factors to obtain optimal and clinically effective cerebrospinal fluid (CSF) araC concentrations. A concentration of araC above 1 μg/mL in CSF, which was lethal to cells in culture, was obtained by intravenous infusion of more than 2,000 mg/m2 of araC for four hours. We propose that araC 2,000 mg/m2 by constant intravenous infusion is preferable in the treatment of leukemia and is associated with the fewest side effects.