Rapoport S I, Fitzhugh R, Pettigrew K D, Sundaram U, Ohno K
Am J Physiol. 1982 Mar;242(3):R339-48. doi: 10.1152/ajpregu.1982.242.3.R339.
A four-compartment model was derived to analyze drug exchange among cerebral capillary plasma, cerebrospinal fluid (CSF), and the brain extracellular and intracellular (or bound) compartments. Equations that were derived incorporated the factor of cerebral blood flow. They were fit by nonlinear least squares to measured brain, plasma, and CSF (when available) concentrations of [14C]urea in the rat, in response to a step increase in plasma concentration, to intravenous infusion, or to a bolus injection of tracer. Best-fit values for the transfer constants were consistent among the three administrative regimens and agreed with published values, when available. Expressions also were derived and numerically evaluated for the lower limit of the brain extracellular space, for half times of brain [14C]urea uptake, and for the steady-state brain/plasma distribution volume. The model should make it possible to use transfer constants obtained for a given drug from one study (e.g., constant plasma concentration) to predict brain concentrations from measured plasma concentrations in other acute or chronic studies.
推导了一个四室模型，以分析脑毛细血管血浆、脑脊液（CSF）以及脑细胞外和细胞内（或结合）室之间的药物交换。推导的方程纳入了脑血流量因素。通过非线性最小二乘法将它们拟合到大鼠中[14C]尿素的测量脑、血浆和脑脊液（如有）浓度，以响应血浆浓度的阶跃增加、静脉输注或示踪剂的推注。三种给药方案的转运常数最佳拟合值一致，并且在有可用数据时与已发表的值相符。还推导了脑细胞外间隙下限、脑[14C]尿素摄取半衰期以及稳态脑/血浆分布容积的表达式并进行了数值评估。该模型应能够使用从一项研究（例如恒定血浆浓度）中获得的给定药物的转运常数，根据其他急性或慢性研究中测量的血浆浓度来预测脑浓度。
