Pharmacokinetics of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate in leukemic cells after intravenous and subcutaneous administration of 1-beta-D-arabinofuranosylcytosine.
The concentration of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate was determined in leukemic cells from 5 patients with acute nonlymphoblastic leukemia during treatment with 1-beta-D-arabinofuranosylcytosine (50 mg/sq m every 12 h). The drug was administered both s.c. and i.v. (bolus injection) to all patients. After various periods of time, venous blood samples were collected and leukemic cells were isolated by density gradient centrifugation. The intracellular concentration of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate was assayed by high-performance liquid chromatography. The peak concentration of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate was significantly higher after s.c. injection than after i.v. injection (P less than 0.05). The area under the concentration versus time curve was twice as large after s.c. injection as it was after i.v. injection (P less than 0.01). The results are consistent with clinical findings indicating that the therapeutic effect of 1-beta-D-arabinofuranosylcytosine is better when it is administered s.c. than when given as i.v. bolus injections.
D000368:Aged; D001085:Arabinofuranosylcytosine Triphosphate / Q000378:metabolism*; D001088:Arabinonucleotides / Q000378:metabolism*; D003561:Cytarabine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007700:Kinetics; D007938:Leukemia / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation
D001088:Arabinonucleotides; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate