Intracellular Pharmacokinetics of Cytosine Arabinoside in Leukemic and Normal Blood Cells

  • E. Schleyer
  • M. Zühlsdorf
  • C. Rolf
  • U. Kewer
  • C. Uhrmeister
  • B. Wörmann
  • T. Büchner
  • W. Hiddemann
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 34)

Abstract

The cytotoxic activity of ara-C has been shown to depend on its intracellular phosphorylation and the accumulation of its active metabolite ara-C 5’ triphosphate (ara-CTP). Especially during high-dose regimens a long ara-CTP retention time was found to be related to the likelihood of achieving a complete remission and possibly even with remission duration [1–3]. These findings provided the means for a pharmacologically directed design of ara-C therapy attempting to optimize dose rates and treatment schedules according to the intracellular pharmacology of ara-CTP in leukemia blasts [4–7]. Preliminary data indicate that the investigation of intracellular ara-C pharmacokinetics may also enable the cytotoxic specificity of ara-C to be increased against leukemic cells since non-leukemic mononuclear cells were found to accumulate less ara-CTP and to eliminate it more rapidly than leukemic blasts. These findings may result from quantitative differences in the deoxyribonucleotide metabolism between the two cell populations as recently suggested by Bhalla and coworkers and Grant et al. [8–9]. The current study was initiated to expand on these investigations and to search for differences in intracellular ara-C pharmacokinetics between leukemic and nonleukemic mononuclear blood cells.

Keywords

Leukemia Oncol Pyrimidine Nucleoside Cytosine 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • E. Schleyer
  • M. Zühlsdorf
  • C. Rolf
  • U. Kewer
  • C. Uhrmeister
  • B. Wörmann
  • T. Büchner
  • W. Hiddemann

There are no affiliations available

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