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.