Cellular pharmacology and optimal therapeutic concentrations of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate in leukemic blasts during treatment of refractory leukemia with high-dose 1-beta-D-arabinofuranosylcytosine.
Cellular pharmacology and optimal therapeutic concentrations of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate in leukemic blasts during treatment of refractory leukemia with high-dose 1-beta-D-arabinofuranosylcytosine.
复制标题
用高剂量 1-β-D-阿拉伯呋喃糖基胞嘧啶治疗难治性白血病期间，白血病母细胞中 1-β-D-阿拉伯呋喃糖基胞嘧啶 5-三磷酸的细胞药理学和最佳治疗浓度。
DOI：
10.1111/j.1600-0609.1986.tb01590.x
复制
发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Keating,MJ
中科院分区：
文献类型：
--
作者：
Plunkett,W;Iacoboni,S;Keating,MJ
本文研究了1-β-D-阿拉伯呋喃胞苷5‘-三磷酸(Ara-CTP)在大剂量单药阿糖胞苷(Ara-C)治疗难治性白血病过程中的药理作用。间歇大剂量阿糖胞苷(3g/m2×4-12剂)治疗有效的患者原始细胞中阿糖胞苷谷值的中位数为196μM，而75μM是区分完全缓解和治疗失败的最低谷浓度(p=0.03)。对大剂量持续输注方案(每12小时2次3g/m2，然后连续输注330-3000 mg/m2×4d)有反应的患者的中位稳态Ara-CTP浓度聚集在79到206μM之间。治疗失败的值主要在这个范围之外(p<；0.005)。提示阿糖胞苷治疗难治性白血病的最佳细胞内浓度范围为75~200μM。
The pharmacology of 1‐β‐D‐arabinofuranosylcytosine 5′‐triphosphate (ara‐CTP) has been studied in the circulating leukemic blasts of patients with refractory leukemia during therapy with high doses of single‐agent ara‐C. Cellular ara‐CTP was analyzed by high‐pressure liquid chromatography. The median trough concentrations of ara‐CTP in blasts of patients who responded to intermittent high‐dose ara‐C (3 g/m2× 4–12 doses) was 196 μM, whereas 75 μM was the lowest trough ara‐CTP concentration that discriminated between complete remission and treatment failure (p=0.03). The median steady state ara‐CTP concentrations in the blasts of patients who responded to a high dose continuous infusion protocol (2 doses of 3 g/m2every 12 hr followed by a continuous infusion of 330–3000 mg/m2× 4 d) were clustered between 79 and 206 μM. The values of treatment failures were predominantly outside this range (p<0.005). These results suggest that the optimal concentration range for intracellular ara‐CTP in the treatment of refractory leukemia may be 75 to 200 μM.