Abstract
Low doses of cytosine arabinoside (ara-C) have recently been administered by intravenous (IV) infusion and intermittent subcutaneous (SC) injection to patients with pre-leukemia and acute leukemia. Our studies have demonstrated that the continuous IV infusion of low-dose (20 mg/m2/d) ara-C produces hematologic improvement in patients with preleukemic syndromes. The present work has monitored plasma ara-C levels in five of these patients. The results demonstrate mean steady- state plasma levels ranging from 1.8 to 6.9 X 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 X 10(-6) mol/L X hour. These findings have been compared to the pharmacokinetics of ara-C (10 mg/m2) given by bolus SC injection. This dose schedule resulted in peak ara-C levels 15 minutes after injection that were tenfold to 30-fold higher than the mean plasma level achieved during continuous IV infusion in the same patient. Furthermore, there was no detectable plasma ara-C at six hours after bolus injection. The differences in ara-C pharmacology for the continuous IV infusion and bolus SC injection dose schedules may contribute to the variability in response and toxicity achieved with these regimens.
