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.
Plunkett
W
W
Department of Medical Oncology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston.
Grindey
G B
GB
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