DRUG TRANSPORT IN BRAIN

顺铂在大鼠脑内的转运和反应已被研究 调查的目的是为了改进相关的 参数 需要这些参数来前瞻性地模拟各种 肿瘤治疗模式的预期疗效。 稳态反应扩散模型能够代表 小脑中的总铂浓度曲线 连续7天输注药物。 输注液套管被视为 点源和流入CSF的药物可忽略不计。 顺铂与细胞的含硫部分的反应是 详细检查。 结合位点的饱和，主要由 半胱氨酸，蛋氨酸，和一些组氨酸残基，发现发生 套管头端1 mm内。 饱和度近似建模为 游离顺铂与时间平均的未结合蛋白质的反应 浓度. 在远离套管的距离处，例如4 mm，蛋白质 含铂的降解产物开始对总 铂概况，但他们被证明只占约3%，没有 超过20%的人出席。 顺铂与蛋白质的最佳线性反应速率为 .005.002 min（-1）。 包括套管头端附近的对流效应 降低该值，但不超过30%，而饱和效应 会增加40%左右 毛细血管通透性被发现， 等于9.0 × 10（-7）cm/sec，几乎不受饱和度的影响。

The transport and reaction of cisplatin in the brain of the rat has been investigated with the intent of refining estimates of associated parameters. These parameters are needed to prospectively model various tumor treatment modalities for expected efficacy. A steady-state reaction-diffusion model was capable of representing the total platinum concentration profiles in the cerebellum following a continuous 7-day infusion of drug. The infusate cannula was treated as a point source and flow of drug into CSF was shown to be negligible. Reaction of cisplatin with the sulfur-containing moieties of cells was examined in detail. Saturation of binding sites, primarily composed of cysteine, methionine, and some histidine residues, was found to occur within 1 mm of the cannuula tip. Saturation was modeled approximately as the reaction of free cisplatin with the time-averaged unbound protein concentration. At distances far from the cannula, e.g. 4 mm, protein degradation products containing platinum begin to contribute to the total platinum profile but they were shown to account for only about 3% and no more than 20% of the total present. The best linear reaction rate of cisplatin with protein was found to be .005 .002 min(-1). Inclusion of convection effects near the cannula tip decreases this value, but by no more than 30%, while saturation effects tend to increase it by about 40%. The capillary permeability was found to equal 9.0x10(-7) cm/sec and be nearly unaffected by saturation.