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9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate pharmacokinetics in plasma and tumor cells of patients with relapsed leukemia and lymphoma.

Abstract
The pharmacokinetics of 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) in plasma and its biologically active 5'-triphosphate (F-ara-ATP) in leukemic cells obtained from the peripheral blood and bone marrow was evaluated in patients with hematologic malignancies subsequent to the first dose of 20-125 mg/m2 per day for 5 days of F-ara-A 5'-monophosphate (F-ara-AMP) administered as an IV bolus over 30 min. The terminal half-lives of elimination of both F-ara-A (8 h) in plasma and intracellular F-ara-ATP (15 h) were not dependent upon the dose of F-ara-AMP. The area under the concentration X time curves for F-ara-A and F-ara-ATP, on the other hand, were increased in proportion to the prodrug dose. There was a high correlation between F-ara-ATP levels in circulating leukemic cells and those in bone marrow cells aspirated at the same time. DNA-synthetic capacity of leukemic cells was inversely related to the associated F-ara-ATP concentration. A linear trend was noted when F-ara-ATP levels in pretreatment peripheral blood leukemic cells incubated with F-ara-A in vitro were compared with the amount of F-ara-A that was incorporated into nucleic acids. Finally, F-ara-ATP concentrations were three times higher in bone marrow cells from patients with lymphomatous bone marrow involvement than from those without evidence of marrow disease.
AuthorsL Danhauser, W Plunkett, M Keating, F Cabanillas
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 18 Issue 2 Pg. 145-52 ( 1986) ISSN: 0344-5704 [Print] Germany
PMID2431803 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antimetabolites, Antineoplastic
  • Arabinonucleotides
  • Vidarabine Phosphate
  • Arabinofuranosylcytosine Triphosphate
  • fludarabine phosphate
  • 2-fluoro-araATP
  • DNA
Topics
  • Antimetabolites, Antineoplastic (metabolism)
  • Arabinofuranosylcytosine Triphosphate (metabolism)
  • Arabinonucleotides (metabolism)
  • DNA (biosynthesis)
  • Humans
  • Kinetics
  • Leukemia (drug therapy, metabolism)
  • Lymphoma (drug therapy, metabolism)
  • Vidarabine Phosphate (analogs & derivatives, metabolism, therapeutic use)

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