Spector R, Spector A Z, Snodgrass S R
Am J Physiol. 1977 Mar;232(3):R73-9. doi: 10.1152/ajpregu.1977.232.3.R73.
A pharmacokinetic model relating the flux of substances between blood, the compartment consisting of the cerebrospinal fluid (CSF)-extracellular space (ECS) of brain, and brain was developed. Transport equations for diffusion, active transport, and bulk flow of CSF between these three compartments were postulated, and kinetic constants were experimentally obtained. The appropriate differential equations were solved on a digital computer to predict concentrations in CSF and brain as a function of the plasma concentration. The ability of the model to predict correctly CSF and brain concentrations of ascorbic acid and mannitol with only knowledge of the plasma concentrations in both steady-state and nonsteady-state conditions was experimentally tested in rabbits. Ascorbic acid was chosen as a model substance that is actively transported into the CSF-ECS of brain and also into brain cells whereas mannitol enters CSF and brain by diffusion. The model made accurate predictions when the assumptions were not violated. Second, the model showed that the experimentally determined Michaelis-Menten transport constant (KT = 0.8 mg=dl-1) for ascorbate transport from blood into the CSF-ECS of brain optimizes ascorbate homeostasis in brain.
建立了一个药代动力学模型，该模型描述了物质在血液、由脑脊髓液（CSF）-脑细胞外间隙（ECS）组成的隔室以及脑之间的通量关系。假定了这三个隔室之间CSF的扩散、主动转运和 bulk flow 的传输方程，并通过实验获得了动力学常数。在数字计算机上求解适当的微分方程，以预测CSF和脑中的浓度作为血浆浓度的函数。在兔子身上通过实验测试了该模型在仅知道稳态和非稳态条件下血浆浓度的情况下正确预测CSF和脑中抗坏血酸和甘露醇浓度的能力。选择抗坏血酸作为一种模型物质，它被主动转运到脑的CSF-ECS中以及脑细胞中，而甘露醇则通过扩散进入CSF和脑。当假设不被违反时，该模型做出了准确的预测。其次，该模型表明，实验确定的抗坏血酸盐从血液转运到脑的CSF-ECS中的米氏转运常数（KT = 0.8 mg=dl-1）优化了脑中抗坏血酸的稳态。
