1. Sequential arabinosylcytosin with or without fludarabine in paracmastic patients with acute myeloid leukemia.
- Author
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Liang A, Zhang H, Fang Y, Li Y, Zhu D, Chen F, Lu H, Fu J, and Bo L
- Subjects
- Adult, Antimetabolites, Antineoplastic cerebrospinal fluid, Antimetabolites, Antineoplastic therapeutic use, Antineoplastic Agents cerebrospinal fluid, Antineoplastic Agents therapeutic use, Area Under Curve, Chromatography, High Pressure Liquid, Cytarabine cerebrospinal fluid, Cytarabine therapeutic use, Drug Interactions, Drug Therapy, Combination, Female, Humans, Indicators and Reagents, Injections, Intravenous, Leukemia, Myeloid, Acute drug therapy, Male, Vidarabine cerebrospinal fluid, Vidarabine pharmacokinetics, Vidarabine therapeutic use, Antimetabolites, Antineoplastic pharmacokinetics, Antineoplastic Agents pharmacokinetics, Cytarabine pharmacokinetics, Leukemia, Myeloid, Acute metabolism, Vidarabine analogs & derivatives
- Abstract
The purpose of this study is to assess how fludarabine (Fa) influences arabinosylcytosin's (Ara-C) mode of action. Plasma, cerebrospinal and urine samples were withdrawn from two study groups at specific time points and analyzed by HPLC. Group A was treated with Ara-C only whereas Group B was treated with Fa+Ara-C. The two study groups are all undergoing complete remission (CR). The Ara-C dose for Group A was 3g/m2 x 2, and the AUC(0-4) was 5.131 +/- 0.936. The Ara-C dose for Group B was 2g/m2 x 2, and the AUC(0-4) was 12.245 +/- 3.863. The AUC(0-4) for Group B is more than twice the AUC(0-4) for Group A, and these results indicate that Fa conduces a synergistic increase in the concentration and AUC of Ara-C in plasma and in cerebrospinal fluid. The pharmacokinetics between the different dose treatments was statistically different (P = 0.016). The differences in the ratios of C(Ara-u) to C(Ara-C), and in the Tmax between Groups A and B could indicate whether or not Ara-C combined with Fa. Although Group B demonstrates a higher AUC(0-4) with lower doses of Ara-C (2 g/m2 x 2), the adverse drug reaction (ADR) and bone inhibition were not more pronounced in Group B compared to Group A. These results are based on a limited number of case studies, hence, additional studies are necessary to support and prove this hypothesis.
- Published
- 2012