PHARMACOKINETICS OF LOW-DOSE 1-BETA-D-ARABINOFURANOSYLCYTOSINE GIVEN BY CONTINUOUS INTRAVENOUS-INFUSION OVER 21 DAYS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (12) , 6498-6501
Abstract
The pharmacokinetic parameters of low dose 1-.beta.-D-arabinofuranosylcytosine (ara-C) infusions were studied in 11 patients, 6 males and 5 females, with a mean age of 68.5 .+-. 13.8 (SD) years. The drug was infused to 4 patients with pre-leukemia (refractory anemia with excess blasts), 5 patients with acute myelogenous leukemia, and 2 patients with secondary leukemia due to chemotherapy, at a dosage of 20 mg/M2/day over 21 days. The patients'' blood and urine wre analyzed for ara-C content by radioimmunoassay. Mean steady state plasma levels of 7.7 .+-. 4.7 ng/ml (31.7 .+-. 19.3 nM) (n = 189) and a range 0.6 (2.5 nM) (lower limit of assay) to 29.7 ng/ml (122.1 nM), with significant inter- and intra-patient variations, were reached within about 2.7 h. The plasma levels of ara-C decreased rapidly, with a t1/2/.alpha. of about 12 min following discontinuation of the infusion, followed by a slow t1/2.beta. of about 19 h. Other parameters (mean values of 10 or 11 patients) were: area under the curve, 182.1 .+-. 64.8 ng .times. day/ml; total body clearance, 188.7 .+-. 54.8 liters/h; renal clearance, 3.1 .+-. 1.4 liters/h; volume of distribution at steady state, 53,913 .+-. 17,626 liters; and recovery of ara-C in urine, 1.43 .+-. 0.69% (n = 226) of daily administered ara-C. A linear relationship was observed with administered dose when the mean plasma levels of our study were compared with the ones reported for conventional ara-C infusions. Plasma clearance was comparable to that observed in conventional dose, when the observed values were extrapolated to the dose administered in this study.