Effects of high-dose cytarabine

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Abstract
Plasma, urine, CSF and tear concentrations of [the antineoplastic drug] cytarabine (ara-C) were measured in 15 patients receiving 3 gm/m2 i.v. ara-C given as a 1 h infusion every 12 h for 6 days. The 2 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 mM) after high-dose therapy were 50 times those achieved with more conventional (100-300 mg/m2) doses. High doses of ara-C were not sufficient to saturate cytidine deaminase; plasma ara-C half-lives (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. CSF ara-C concentrations after high-doses (.hivin.x = 7.8 .mu.M) were 10 times those after conventional i.v. dosing, but were 0.5%-1.0% those achieved by intrathecal ara-C doses. Tear concentrations of 22 and 38 .mu.M were measured in 2 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.