Pharmacokinetics of the 5'-triphosphates of arabinosylcytosine and 2',2'-difluorodeoxycytidine in L1210 cells.
The clinical efficacy of ara-C is limited by a rapid elimination of the active triphosphate by target cells. The nucleoside antimetabolite, 2',2'-difluorodeoxycytidine, accumulates in leukemia cells as the respective 5'-triphosphate dFdCTP. In contrast to ara-C triphosphate, dFdCTP is eliminated with biphasic kinetics that exhibit a terminal half-life that approaches the cell cycle time. The cellular pharmacokinetics of dFdCTP may explain the unusual dose schedule and spectrum of efficacy against murine tumors.
Department of Medical Oncology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston.
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Plunkett
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Grindey
D000818:Animals; D001085:Arabinofuranosylcytosine Triphosphate / Q000378:metabolism*; D001088:Arabinonucleotides / Q000378:metabolism*; D001692:Biological Transport; D003561:Cytarabine; D003570:Cytidine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D003597:Cytosine Nucleotides; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D013329:Structure-Activity Relationship
D001088:Arabinonucleotides; D003597:Cytosine Nucleotides; D003561:Cytarabine; C054403:2',2'-difluorodeoxycytidine 5'-triphosphate; D001085:Arabinofuranosylcytosine Triphosphate; D003570:Cytidine Triphosphate