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ACNU在脑肿瘤中的药代动力学分析(作者译)

[Pharmacokinetic analysis of ACNU in brain tumors (author's transl)].

作者信息

Hara M, Takeuchi K

出版信息

No To Shinkei. 1979 Dec;31(12):1289-93.

PMID:526372
Abstract

In order to establish the standard of administration of ACNU against brain tumors, pharmacokinetic analysis of ACNU in tumor tissue, cystic fluid, cerebrospinal fluid and blood was performed. The sample specimens were obtained sequentially after intravenous administration of 1--2 mg/kg/BW of ACNU and quantitatively analysed by high-performance liquid chromatography in 3 cases of glioblastoma and each one case of astrocytoma, meningioma and brain metastasis. Concentrations of ACNU in blood was calculated by two compartment open model and those in cystic fluid was calculated by one compartment model using BMDP-3R program. The half-time in blood was 2.6--4.1 min, and its distribution was very fast. The penetration of ACNU into the tumor tissue was sufficient, because the central compartment was 23% and the tissue compartment was 77%. The transmission rate constant into the cyst was 1.8 and the elimination rate constant was 0.96. The maximum concentration in the cystic fluid 42 min after intravenous injection of 2 mg/kg/BW of ACNU was 0.27--0. 35 mg/dl. In conclusion, 3--4 mg/kg/BW of ACNU should be injected intravenously at one time.

摘要

为确立阿糖胞苷治疗脑肿瘤的用药标准,对3例胶质母细胞瘤、各1例星形细胞瘤、脑膜瘤及脑转移瘤患者静脉注射1-2mg/kg体重的阿糖胞苷后,依次采集肿瘤组织、囊液、脑脊液及血液样本,采用高效液相色谱法进行定量分析。利用BMDP-3R程序,通过二室开放模型计算血液中阿糖胞苷的浓度,通过一室模型计算囊液中阿糖胞苷的浓度。血液中阿糖胞苷的半衰期为2.6-4.1分钟,其分布非常迅速。阿糖胞苷向肿瘤组织的渗透充分,因为中央室占23%,组织室占77%。进入囊腔的传输速率常数为1.8,消除速率常数为0.96。静脉注射2mg/kg体重的阿糖胞苷42分钟后,囊液中的最大浓度为0.27-0.35mg/dl。综上所述,应一次性静脉注射3-4mg/kg体重的阿糖胞苷。

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