Pharmacokinetics of low-dose 1-β-D-arabinofuranosylcytosine given by continuous intravenous infusion over twenty-one days

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...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 1985-12, Vol.45 (12), p.6498-6501
Hauptverfasser: KREIS, W, FARIDA CHAUDHRI, CHAN, K, ALLEN, S, BUDMAN, D. R, SCHULMAN, P, WEISELBERG, L, FREEMAN, J, DEERE, M, VINCIGUERRA, V
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Sprache:eng
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Zusammenfassung: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 were 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 very slow t 1/2 beta of about 19 h. Other parameters (mean values of 10 or 11 patients) were: area under the curve, 182.1 +/- 64.8 ng X 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.
ISSN:0008-5472
1538-7445