DRUG TRANSPORT IN BRAIN

微量输注进入脑组织的理论传输模型已被 发达的，将大脑视为刚性的或可变形的弹性体 小分子或大分子溶液进入的介质 流速为0.1~6.0亩(1)/分钟。刚性孔隙理论 给出了浓度分布的一个简单表达式 灰质中的大分子，距离达1.5-2厘米，超过 由于Peclet数较高，采用了扩散/整体相结合的模型。 灰质与植物血凝素的实验证实了 正确数量级的注入物的球形扩散。低- 顺应性导管被设计成提供小输液量 (约1(亩)1)；这些导管输送营养因子 在整个大鼠灰质中，允许物质转移到 黑质。建立了孔洞弹性变形模型。 它标识了描述所需参数的关键组合 均匀组织中的变形。输液后弥散松弛 已被证明是药效学效应的一个强有力的决定因素。一个 12小时大流量输液可增加穿透距离。 低流量技术0.3-1.0厘米，视降解率而定，当 在固定的药效学指标下进行比较。

Theoretical transport models of microinfusion into brain tissue have been developed, treating the brain either as a rigid or deformable elastic medium into which small molecular weight or macromolecular solutions are infused at flow rates from 0.1 to 6.0 mu(1)/min. Rigid pore theory yielded a simple expression for the concentration profile of macromolecules in grey matter for distances up to 1.5-2 cm, beyond which combined diffusion/bulk models were used because of high Peclet number. Grey matter experiments with phytohemagglutinin have confirmed a spherical spread of infusate of the correct order of magnitude. Low- compliance catheters have been designed to deliver small infusate volumes (approximately 1(mu)1); these catheters delivered trophic factors throughout rat grey matter, allowing transfer of material to the substantia nigra. A poroelastic deformation model has been completed which identifies key combinations of parameters required to describe deformation in homogeneous tissue. Postinfusion diffusional relaxation has been shown to be a strong determinant of pharmacodynamic effect. A 12-hr high-flow infusion was shown to increase penetration distance over low-flow technology by 0.3-1.0 cm, depending on degradation rate, when compared at a fixed pharmacodynamic metric.