Cytosine arabinoside cerebrospinal fluid kinetics
Cytosine arabinoside cerebrospinal fluid kinetics
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胞嘧啶阿糖苷脑脊液动力学
DOI：
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发表时间：
1984
期刊：
影响因子：
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通讯作者：
D. Poplack
中科院分区：
文献类型：
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作者：
S. Zimm;J. Collins;J. Miser;D. Chatterji;D. Poplack
为了更好地表征阿糖胞苷（Ara-C）在脑脊液（CSF）中的分布，在7例完全缓解的脑膜白血病患者中研究了其动力学。脑室内注射30 mg Ara-C后，在24小时内采集CSF和血浆样本。通过反相HPLC测定法（CSF中灵敏度为0.5µM，血浆中灵敏度为1.0 µM）测量Ara-C水平，该方法可将Ara-C与其主要代谢产物尿嘧啶阿拉伯糖苷（Ara-U）分离。CSF中Ara-C的消除遵循双相模式，初始t1/2为1小时，终末t1/2为3.4小时。CSF中Ara-C的清除率为0.42 ml/min，表明药物主要通过CSF整体流动消除。Ara-U的AUC与Ara-C的AUC的比值为0.08，表明与全身性Ara-C给药后相比，CSF中Ara-C仅少量代谢为Ara-U。尽管初始CSF Ara-C浓度超过2 mM，但在任何患者的血浆中均未检测到Ara-C。脑室内Ara-C导致CSF中的水平非常高，但全身组织相对免于暴露于Ara-C。
To better characterize the disposition of cytosine arabinoside (Ara‐C) in cerebrospinal fluid (CSF), its kinetics were studied in seven patients with meningeal leukemia in complete remission. After intraventricular injection of 30 mg Ara‐C, CSF and plasma samples were obtained over a 24‐hr period. Ara‐C levels were measured by a reverse‐phase HPLC assay (with a sensitivity of 0.5µM in CSF and 1.0 µM in plasma) that readily separated Ara‐C from its major metabolite uracil arabinoside (Ara‐U). Elimination of Ara‐C from CSF followed a biphasic pattern, with an initial t½ of 1 hr and a terminal t½ of 3.4 hr. Ara‐C clearance from CSF was 0.42 ml/min, suggesting that drug elimination was primarily by CSF bulk flow. The ratio of the AUC of Ara‐U to the AUC of Ara‐C was 0.08, indicating only minor metabolism of Ara‐C to Ara‐U in CSF, in contrast to that after systemic Ara‐C. Despite initial CSF Ara‐C concentrations exceeding 2 mM, Ara‐C was not detectable in plasma in any patient. Intraventricular Ara‐C results in very high levels in CSF, but systemic tissues are relatively spared from exposure to Ara‐C.