Clinical pharmacology of cytarabine in patients with acute myeloid leukemia: a Cancer and Leukemia Group B study
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- Fleming, R.A., Capizzi, R.L., Rosner, G.L. et al. Cancer Chemother. Pharmacol. (1995) 36: 425. doi:10.1007/BF00686192
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The pharmacokinetics of cytarabine (ara-C) were determined in 265 patients with acute myeloid leukemia (AML) receiving ara-C (200 mg/m2 per day for 7 days as a continuous infusion) and daunorubicin during induction therapy. The mean (standard deviation) ara-C concentration at steady-state (Css) and systemic clearance (Cl) were 0.30 (0.13) μM and 134 (71) l/h per m2 respectively. Males had a significantly faster ara-C Cl (139 vs 131 l/h per m2,P=0.025) than females. Significant correlations were noted between ara-C Cl and the pretreatment, peripheral white blood cell count (P=0.005) and pretreatment blast count (P=0.020). No significant differences in ara-C Css or Cl were noted in patients achieving complete remission compared with those failing therapy (P=0.315,P=0.344, respectively). No significant correlations were observed between ara-C pharmacokinetic parameters and several indices of patient toxicity. Our findings indicate that variability in ara-C disposition in plasma at this dosage level does not correlate with remission status or toxicity in patients with AML receiving initial induction therapy with ara-C and daunorubicin.