In-vivo microdialysis study of the distribution of cisplatin into brain tumour tissue after intracarotid infusion in rats with 9L malignant glioma
In-vivo microdialysis study of the distribution of cisplatin into brain tumour tissue after intracarotid infusion in rats with 9L malignant glioma
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DOI：
10.1111/j.2042-7158.1997.tb06111.x
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发表时间：
1997-08-01
影响因子：
3.3
通讯作者：
Ichikawa, M
中科院分区：
文献类型：
--
作者：
Nakashima, M;Shibata, S;Ichikawa, M
为了研究抗癌药物顺铂在大鼠体内的局部分布，采用肿瘤和非肿瘤组织同时脑微透析的方法，将9L恶性胶质瘤移植到大鼠脑内，选择性颈动脉注射顺铂(3.5 mg·kg~(-1))30min。以顺铂为代表，用原子吸收光谱法测定肿瘤和非肿瘤脑组织透析液中铂的含量。同时测定血浆中总铂和游离铂的浓度。脑肿瘤分布系数(脑肿瘤铂AUC与血浆游离铂AUC的比值，其中AUC为铂浓度-时间曲线下面积)为0.69，而在正常脑组织中几乎没有分布。药物与血浆蛋白结合率为65%。结论：同步微透析法是一种简便、有效的评价顺铂体内局部药代动力学及脑内肿瘤和非肿瘤组织分布的方法。
Simultaneous brain microdialysis in tumour and non-tumour tissues has been used for kinetic determination of the local distribution of an anticancer agent, cisplatin, in rats.Rat brain was implanted with 9L malignant glioma and cisplatin (3.5 mg kg(-1)) was administered as a selective intracarotid infusion for 30 min to rats prepared for brain microdialysis. The amount of platinum in the dialysate collected from tumour and non-tumour brain tissues was determined by atomic absorption spectrophotometry, as representative of cisplatin. Total and free platinum concentrations in plasma were also measured. Free platinum is accumulated preferentially in the tumour tissue and the brain tumour distribution coefficient (the ratio of brain tumour platinum AUC to plasma free platinum AUG, where AUC is the area under the platinum concentration-time curve) was 0.69, although there was little distribution into normal brain tissue. Drug binding to plasma proteins was 65%.It is concluded that simultaneous microdialysis is an easy and available method for assessing in-vivo local pharmacokinetics and distribution of cisplatin in tumour and non-tumour tissues of the brain.