Relationship of 1-β-d-Arabinofuranosylcytosine in Plasma to 1-β-d-Arabinofuranosylcytosine 5′-Triphosphate Levels in Leukemic Cells during Treatment with High-Dose 1-β-d-Arabinofuranosylcytosine

摘要: The pharmacokinetic values of 1-β-d-arabinofuranosylcytosine (ara-C) in plasma and its active metabolite 5′-triphosphate (ara-CTP) circulating blast cells were studied 11 patients with acute leukemia. ara-C was administered as a 2-h infusion (3 g/m2) followed 12 to 24 h by continuous for 4 days 10 7 one. A steady-state concentration (94 ± 32 µm) reached the end infusion. Its elimination biphasic an initial terminal t v2 0.44 0.10 2.8 0.9 h, respectively. accumulation ara-CTP leukemic linear continued up 2 after bolus monophasic median 3.4 (range, 1.25 18.9 h). disposition 1-β-d-arabinofuranosyluracil during dose rate over range 70 3000 mg/m2/day. area under versus time curve not related infused, but rather appeared be intrinsic each individual. As general finding, blasts more heterogeneous than those plasma. There marked differences absolute concentrations at different times also No correlation evident between determinants ara-CTP. Thus, it is concluded that pharmacokinetics cannot predict metabolism cells.