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
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
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高剂量 1-β-d-阿拉伯呋喃糖基胞嘧啶治疗期间血浆中 1-β-d-阿拉伯呋喃糖基胞嘧啶与白血病细胞中 1-β-d-阿拉伯呋喃糖基胞嘧啶 5-三磷酸水平的关系
DOI：
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
D. Dixon
中科院分区：
文献类型：
--
作者：
J. Liliemark;W. Plunkett;D. Dixon
本文研究了11例急性白血病患者血浆中1-β-d-阿拉伯呋喃胞苷(Ara-C)及其活性代谢物1-β-d-阿拉伯呋喃胞苷5‘-三磷酸(Ara-CTP)的药代动力学。阿糖胞苷(Ara-C)静脉滴注2 h(3g/m2)，12~24 h后持续滴注4 d，1例7 d。静脉滴注2小时后，血浆中阿糖胞苷达到稳态浓度(94±32µm)。消除为双相，起始和终止的tv2分别为0.44±0.10h和2.8±0.9h。Ara-CTP在白血病细胞中的蓄积呈线性，并持续到团注后2小时。Ara-CTP的消除是单相的，中位tv2为3.4h(1.25~18.9h)。阿糖胞苷和1-β-d-阿糖尿嘧啶在持续输注过程中的分布与剂量率在70~3000 mg/m~2/d范围内呈线性关系。白血病细胞中Ara-CTP浓度-时间曲线下的面积与输注剂量无关，而似乎是每个人细胞所固有的。作为一个普遍的发现，Ara-CTP在循环母细胞中的药代动力学值比在血浆中的Ara-C更不均匀。给药后不同时间和持续给药过程中，血浆中Ara-C和白血病细胞中Ara-CTP的绝对浓度均有显著差异。Ara-C药代动力学的决定因素和Ara-CTP的决定因素之间没有明显的相关性。因此，阿糖胞苷在血浆中的药代动力学不能预测阿糖胞苷在白血病细胞中的代谢。
The pharmacokinetic values of 1-β-d-arabinofuranosylcytosine (ara-C) in plasma and its active metabolite 1-β-d-arabinofuranosylcytosine 5′-triphosphate (ara-CTP) in circulating blast cells were studied in 11 patients with acute leukemia. ara-C was administered as a 2-h infusion (3 g/m2) followed in 12 to 24 h by a continuous infusion for 4 days in 10 patients and for 7 days in one. A steady-state concentration of ara-C in plasma (94 ± 32 µm) was reached by the end of the 2-h infusion. Its elimination was biphasic with an initial and terminal t v2 of 0.44 ± 0.10 h and 2.8 ± 0.9 h, respectively. The accumulation of ara-CTP in leukemic cells was linear and continued for up to 2 h after the bolus infusion. ara-CTP elimination was monophasic with a median t v2 of 3.4 h (range, 1.25 to 18.9 h). The disposition of ara-C and 1-β-d-arabinofuranosyluracil during continuous infusion was linear with dose rate over the dose range of 70 to 3000 mg/m2/day. The area under the concentration versus time curve for ara-CTP in leukemic cells was not related to the dose infused, but rather appeared to be intrinsic to the cells of each individual. As a general finding, the pharmacokinetic values of ara-CTP in circulating blasts were more heterogeneous than those of ara-C in plasma. There were marked differences in the absolute concentrations of ara-C in plasma and ara-CTP in leukemic cells at different times after the bolus infusion and also during continuous infusion. No correlation was evident between the determinants of ara-C pharmacokinetic values and those of ara-CTP. Thus, it is concluded that the pharmacokinetics of ara-C in plasma cannot predict for the metabolism of ara-CTP in leukemic cells.
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DOI：
10.1200/jco.1984.2.10.1092
发表时间：
1984
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
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影响因子：
11.2
作者：
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影响因子：
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DOI：
10.1002/mpo.2950100706
发表时间：
1982
期刊：
Medical and pediatric oncology
影响因子：
--
作者：
Rustum,YM;Slocum,HK;Wang,G;Bakshi,D;Kelly,E;Buscaglia,D;Wrzosek,C;Early,AP;Preisler,H
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影响因子：
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作者：
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