PHARHACOKINETIC STUDIES ON ARA‐C

Abstract

SUMMARYPharmacokinetic studies of ara‐C in plasma are reviewed. The value of monitoring ara‐C in plasma is limited, because ara‐C is an inactive prodrug, and has to be phosphorylated to ara‐CTP intracellularly to excert its activity. Therefore, the pharmacokinetics of ara‐CTP in leukemic cells was studied. The differences between the pharmacokinetics of ara‐C in plasma and ara‐CTP in leukemic cells in terms of elimination rates and heterogeneity are important and there seems to be only poor correlation between the two. This is the rational for attempts to correlate the pharmacokinetics of cellular ara‐CTP to clinical effect of ara‐C treatment. The accumulation of ara‐CTP seems to be saturated during high‐dose ara‐C treatment. As a consequence, the duration of infusion is a more important determinant of the efficacy than the dose in high‐dose ara‐C treatment. This should be considered in design of high‐dose ara‐C treatment protocols.