Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam.
Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam.
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发表时间：
1993-04
期刊：
影响因子：
11.2
通讯作者：
S. Kim;S. Khatibi;Stephen B. Howell;C. McCully;F. Balis;D. Poplack
中科院分区：
文献类型：
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作者：
S. Kim;S. Khatibi;Stephen B. Howell;C. McCully;F. Balis;D. Poplack
使用细胞周期特异性抗代谢物对软脑膜白血病或癌病进行最佳治疗时，需要在脑脊液中长期维持治疗药物浓度。本文研究了1-β-D-阿拉伯呋喃糖基胞嘧啶（ara-C）包封在DepoFoam（Depo/Ara-C）中的药物动力学。单次给药2 mg后，Depo/Ara-C浓度呈双指数下降，初始和终末半衰期分别为14.6和156 h。游离药物浓度保持高于报告的最低细胞毒性水平0.1微克/毫升（0.4 μ M）超过672小时（28天）。相比之下，在一只动物中腰椎内推注剂量的未包封的药物后，阿糖胞苷的半衰期为0.74小时。单次鞘内注射Depo/Ara-C可以在很长一段时间内维持脑脊液中的治疗药物浓度。
Prolonged maintenance of a therapeutic drug concentration in the cerebrospinal fluid is required for optimal treatment of leptomeningeal leukemia or carcinomatosis with cell cycle-specific antimetabolites. The pharmacokinetics of 1-beta-D-arabinofuranosylcytosine (ara-C) encapsulated into DepoFoam (Depo/Ara-C) was studied in six rhesus monkeys after intrathecal injection into the lumbar sac. Following a single 2-mg dose, the Depo/Ara-C concentration decreased biexponentially with initial and terminal half-lives of 14.6 and 156 h, respectively. The free drug concentration remained above the reported minimal cytotoxic level of 0.1 micrograms/ml (0.4 microM) for more than 672 h (28 days). In contrast, the half-life of ara-C following an intralumbar bolus dose of unencapsulated drug in a single animal was 0.74 h. A single intrathecal injection of Depo/Ara-C can maintain a therapeutic drug concentration in the cerebrospinal fluid for a very prolonged period.