[Is the pharmacokinetic profile of cytarabine clinically relevant?]

Cytarabine (Ara-C) is a cytotoxic agent which is rapidly metabolized and thus has a short half-life. Consequently, variations of infusion time influence directly the plasma level over time. Individual differences in plasma level courses with identical dosage are irrelevant regarding treatment response. Several studies, however, reported correlation of the leukemic cells' ability to build and retain the metabolite Ara-C-triphosphate (Ara-CTP) intracellularly with clinical response to therapy. The half-life of the intracellular Ara-CTP concentration in myelogenic blasts (AML) is lower than in blasts from children with acute lymphoblastic leukemia (common-ALL). The varying dosage recommendations of conventional (CD), intermediate (ID) and high-dose (HD) Ara-C therapy are based on considerations of cellular pharmacology. ID and HD Ara-C therapy schedules are designed to overcome well-known resistance phenomena thus providing high intracellular Ara-CTP concentrations.