Sequential arabinosylcytosin with or without fludarabine in paracmastic patients with acute myeloid leukemia.
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 Plasma, cerebrospinal and urine samples were withdrawn from two study groups at specific time points and analyzed by HPLC.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.
Department of Clinical Pharmacology, Tongji Hospital, Tongji University School of Medicine, China.
Aibin
A
Liang
Hong
H
Zhang
Yu
Y
Fang
Ying
Y
Li
Deqiu
D
Zhu
Fangyuan
F
Chen
Huina
H
Lu
Jianfei
J
Fu
Lanjun
L
Bo
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003561:Cytarabine / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine