CLINICAL-PHARMACOLOGY OF LOW-DOSE CYTOSINE-ARABINOSIDE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 65  (5) , 1087-1089
Abstract
Low doses of cytosine arabinoside (ara-C) were recently administered by IV infusion and intermittent s.c. injection to patients with preleukemia and acute leukemia. The continuous IV infusion of low-dose (20 mg/m2/d) ara-C apparently produces hematologic improvement in patients with preleukemic syndromes. The present work has monitored plasma ara-C levels in 5 of these patients. The results demonstrate mean steady-state plasma levels ranging from 1.8 to 6.9 .times. 10-8 mol/l. The range for total drug exposure (area under the curve) for the 14-day course was 6.5 to 15.9 .times. 10-6 mol/l .times. h. These findings were compared to the pharmacokinetics of ara-C (10 mg/m2) given by bolus s.c. injection. This dose schedule resulted in peak ara-C levels 15 min after injection that were 10-fold to 30-fold higher than the mean plasma level achieved during continuous IV infusion in the same patient. There was no detectable plasma ara-C at 6 h after bolus injection. The differences in ara-C pharmacology for the continuous IV infusion and bolus s.c. injection dose schedules may contribute to the variability in response and toxicity achieved with these regimens.