DRUG TRANSPORT IN BRAIN

显微输注进入脑组织的理论运输模型已经建立

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.