Slevin M L, Piall E M, Aherne G W, Harvey V J, Johnston A, Lister T A
J Clin Oncol. 1983 Sep;1(9):546-51. doi: 10.1200/JCO.1983.1.9.546.
The pharmacokinetics of high-dose cytosine arabinoside (ara-C) were studied in 18 patients with acute leukemia and high-grade non-Hodgkin's lymphoma. The plasma concentrations of ara-C increased in proportion to the dose over a range of 1-3 g/m2. The initial and terminal half-lives were not influenced by the dose or schedule of administration and no accumulation of ara-C occurred with repeated dosage in the same patients. These data suggest that cytidine deaminase is not saturated within this dose range. The cerebrospinal fluid (CSF) concentrations of ara-C also rose linearly with the increase in dose and varied from 347 ng/mL (1 g/m2) to 1,070 ng/mL (3 g/m2). The mean CSF concentrations of ara-C following high-dose infusions over three hours were 6%-22% of simultaneous plasma concentrations. Three hours after completion of the intravenous infusion the CSF concentrations were greater than the corresponding plasma concentrations owing to the long half-life of ara-C in CSF compared to that in plasma. These data demonstrate that therapy with intravenous high-dose ara-C given twice daily provides continuous levels in the CSF at concentrations that are likely to be of value in the treatment of central nervous system leukemia.
对18例急性白血病和高级别非霍奇金淋巴瘤患者研究了大剂量阿糖胞苷（ara-C）的药代动力学。在1-3 g/m²剂量范围内，ara-C的血浆浓度与剂量成正比增加。初始半衰期和终末半衰期不受给药剂量或给药方案的影响，同一患者重复给药未出现ara-C蓄积。这些数据表明，在此剂量范围内胞苷脱氨酶未饱和。ara-C的脑脊液（CSF）浓度也随剂量增加呈线性上升，范围从347 ng/mL（1 g/m²）至1070 ng/mL（3 g/m²）。大剂量输注3小时后，ara-C的平均CSF浓度为同期血浆浓度的6%-22%。静脉输注完成3小时后，由于ara-C在CSF中的半衰期比在血浆中长，CSF浓度高于相应的血浆浓度。这些数据表明，每日两次静脉给予大剂量ara-C治疗可使CSF中维持持续浓度，这可能对中枢神经系统白血病的治疗有价值。
