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- W2093426785 abstract "The pharmacology of fludarabine triphosphate (F-ara-ATP) in leukemic lymphocytes was studied during a phase II trial of fludarabine in 24 patients with chronic lymphocytic leukemia (CLL). Fludarabine was given as a 30-min i.v. infusion at a dose of 25 or 30 mg/m2 daily for 5 days. The concentrations of F-ara-ATP, the active metabolite of fludarabine, were determined in leukemic lymphocytes at intervals up to 24 hr after the first infusion. A median peak concentration of 19 microM (range, 6-52 microM) was generally reached 4 hr after the beginning of the infusion. No significant relationship was observed between clinical response and the median peak level of F-ara-ATP or the retention of F-ara-ATP in leukemic lymphocytes. In vitro incubation of CLL cells with the parent nucleoside of fludarabine, arabinosyl-2-fluoroadenine (F-ara-A), indicated that F-ara-ATP accumulated in a linear fashion in response to the product of the F-ara-A concentration times the duration of incubation. Exposing cells longer with lower F-ara-A concentrations or shorter with higher F-ara-A concentrations resulted in similar intracellular levels of F-ara-ATP as long as the products of fludarabine concentration and time of exposure were equal. These results and the fact that the fludarabine dose rate currently administered is well tolerated suggest that it may be the optimal dose rate for F-ara-ATP accumulation in CLL cells." @default.
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- W2093426785 date "1993-01-01" @default.
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- W2093426785 title "Cellular Pharmacology of Fludarabine Triphosphate in Chronic Lymphocytic Leukemia Cells During Fludarabine Therapy" @default.
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- W2093426785 doi "https://doi.org/10.3109/10428199309147356" @default.
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