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  • Title: Effects of high-dose cytarabine.
    Author: Hande KR, Stein RS, McDonough DA, Greco FA, Wolff SN.
    Journal: Clin Pharmacol Ther; 1982 May; 31(5):669-74. PubMed ID: 7075116.
    Abstract:
    Plasma, urine, cerebrospinal fluid, and tear concentrations of cytarabine (ara-C) were measured in 15 patients receiving 3 gm/m2 IV ara-C given as a 1 hr infusion every 12 hr for 6 days. The two assay methods used for measuring ara-C concentrations (high-pressure liquid chromatography and radioimmunoassay) gave much the same results. Peak plasma ara-C concentrations (2.0 microM) after high-dose therapy were 50 times those achieved with more conventional (100 to 300 mg/m2) doses. High doses of ara-C were not sufficient to saturate cytidine deaminase; plasma ara-C half-lifes (t1/2) after high-dose therapy (distribution t1/2 = 6.2 min; elimination t1/2 = 154 min) were much the same as those after conventional ara-C doses. Kinetics of ara-C were not altered by repeated dosing over a 6-day period. Cerebrospinal fluid ara-C concentrations after high-doses (mean = 7.8 microM) were 10 times those after conventional intravenous dosing, bot were 0.5% to 1.0% those achieved by intrathecal ara-C doses. Tear concentrations of 22 and 38 micro M were measured in two patients who developed conjunctivitis after high-dose therapy so that the presence of ara-C in tears may be a cause of the conjunctivitis seen in some patients.
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