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Leuk Lymphoma. 1997 Oct;27(3-4):321-7.

Pharmacokinetics of high-dose cytarabine and its deamination product--a reappraisal.

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Clinic of Hematology, Oncology and Clinical Immunology, Heinrich Heine University, Düsseldorf, Germany.


Cytarabine is intracellularly activated and correlations have been established between the pharmacokinetic behaviour of active metabolites and their antileukemic effect. Recently, a good response to high-dose treatment of leukemias has additionally been attributed to a so-called low deamination phenotype of cytarabine inactivation. Consequently, these findings would support plasma level monitoring of cytarabine and its metabolite uracil arabinoside in high-dose cytarabine regimens. This pharmacokinetic study presents data attempting to reevaluate these observations. Thirty-seven patients were treated by 3-h high-dose cytarabine infusions (9 patients 1000 mg/m2, 28 patients 3000 mg/m2) as part of their treatment for acute leukemia. Serial blood samples during and post infusion were analysed for cytarabine (araC) and its deamination product uracil arabinoside (araU) using HPLC with UV-detection. Considerable interindividual variation was observed in end-infusion plasma concentrations of araC (1000 mg/m2: 2.1-fold, 3000 mg/m2: 5.5-fold) and araU (1000 mg/m2: 2.7-fold, 3000 mg/m2: 2.9-fold). The median ratio of end infusion concentrations araU/araC (on a molar basis) was 5.6 (S.D. 3.0), extreme ratio values were 2 and 14. No differences of the araU/araC ratio were found between the two dosages used. Minimum plasma araC concentrations at the end of infusion were 10.5 micromol/l and 22.0 micromol/l at a dose of 1000 and 3000 mg/m2, respectively. In our European study population a "fast" deamination phenotype of cytarabine (araU/araC ratio > 14) was not be observed.

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