Veng-Pedersen P, Brashear R E, Karol M D
J Pharm Sci. 1983 Aug;72(8):951-3. doi: 10.1002/jps.2600720830.
A simple diffusion-based pharmacokinetic model is proposed relating blood-brain barrier transfer kinetics of theophylline to the difference in the free concentrations of the drug in serum and cerebrospinal fluid (CSF). The model predicts that the CSF drug level is proportional to the serum drug level convoluted by exp(-kt), where k is the blood-brain barrier diffusion rate constant. An excellent agreement was found by nonlinear regression analysis between serum and CSF theophylline data in eight dogs and the proposed model for the blood-brain barrier transfer kinetics of theophylline. The ratio of the free fractions of theophylline in serum and CSF predicted from the model also agrees with the value determined experimentally.
提出了一种基于简单扩散的药代动力学模型，该模型将茶碱的血脑屏障转运动力学与药物在血清和脑脊液（CSF）中的游离浓度差异相关联。该模型预测，脑脊液中的药物水平与血清药物水平经exp(-kt)卷积后成正比，其中k是血脑屏障扩散速率常数。通过非线性回归分析发现，八只狗的血清和脑脊液茶碱数据与所提出的茶碱血脑屏障转运动力学模型之间具有极佳的一致性。从该模型预测的血清和脑脊液中茶碱的游离分数之比也与实验测定值相符。
