Riva-Lavieille C, Ressayre C, Barra Y, Carcassonne Y, Iliadis A
Faculté de Pharmacie, Groupe de Recherche sur les Cancers des Voies Aériennes, Grenoble, France.
Ther Drug Monit. 1994 Aug;16(4):375-9. doi: 10.1097/00007691-199408000-00007.
Patients with acute nonlymphocytic leukemia (ANLL) were treated by continuous infusion of ara-C (100 mg/m2/d x 10 days). During ara-C treatment, cellular arabinofuranosyl cytosine triphosphate (ara-CTP) pharmacokinetics was assessed in the circulating blasts of these patients using a high-performance liquid chromatography (HPLC) and an associated radioimmunoassay. Since a strong correlation was found between achievement of complete remission and cellular ara-CTP levels, we propose a calculation scheme that allows steady-state adjustment of ara-CTP levels during administration of ara-C. To improve the complete remission rate in patients with low ara-CTP levels, we sought optimum ara-C dosing. In order to achieve an optimal therapeutic response, in vivo ara-CTP formation has to be > 50 microM in leukemic cells. Conversely, using the same pharmacokinetic approach, the infusion rate at which to administer ara-C in order to reach in vivo ara-CTP concentration threshold and to achieve complete remission could be calculated for each patient.
急性非淋巴细胞白血病（ANLL）患者接受阿糖胞苷持续输注治疗（100mg/m²/天，共10天）。在阿糖胞苷治疗期间，使用高效液相色谱法（HPLC）和相关放射免疫测定法评估这些患者循环原始细胞中的细胞阿糖呋喃糖基胞嘧啶三磷酸（ara-CTP）药代动力学。由于发现完全缓解的实现与细胞ara-CTP水平之间存在强相关性，我们提出了一种计算方案，该方案允许在阿糖胞苷给药期间对ara-CTP水平进行稳态调整。为了提高ara-CTP水平低的患者的完全缓解率，我们寻求最佳的阿糖胞苷给药剂量。为了实现最佳治疗反应，白血病细胞中体内ara-CTP的形成必须>50μM。相反，使用相同的药代动力学方法，可以为每位患者计算为达到体内ara-CTP浓度阈值并实现完全缓解而给予阿糖胞苷的输注速率。
