一种确定药物透过血脑屏障能力的方法。
A method to determine the ability of drugs to diffuse through the blood-brain barrier.
作者信息
Seelig A, Gottschlich R, Devant R M
机构信息
Biocenter of the University of Basel, Switzerland.
出版信息
Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):68-72. doi: 10.1073/pnas.91.1.68.
A method has been devised for predicting the ability of drugs to cross the blood-brain barrier. The criteria depend on the amphiphilic properties of a drug as reflected in its surface activity. The assessment was made with various drugs that either penetrate or do not penetrate the blood-brain barrier. The surface activity of these drugs was quantified by their Gibbs adsorption isotherms in terms of three parameters: (i) the onset of surface activity, (ii) the critical micelle concentration, and (iii) the surface area requirement of the drug at the air/water interface. A calibration diagram is proposed in which the critical micelle concentration is plotted against the concentration required for the onset of surface activity. Three different regions are easily distinguished in this diagram: a region of very hydrophobic drugs which fail to enter the central nervous system because they remain adsorbed to the membrane, a central area of less hydrophobic drugs which can cross the blood-brain barrier, and a region of relatively hydrophilic drugs which do not cross the blood-brain barrier unless applied at high concentrations. This diagram can be used to predict reliably the central nervous system permeability of an unknown compound from a simple measurement of its Gibbs adsorption isotherm.
已设计出一种预测药物穿越血脑屏障能力的方法。该标准取决于药物的两亲性质，这在其表面活性中有所体现。使用了各种能穿透或不能穿透血脑屏障的药物进行评估。这些药物的表面活性通过其吉布斯吸附等温线，依据三个参数进行量化：（i）表面活性的起始点，（ii）临界胶束浓度，以及（iii）药物在空气/水界面的表面积需求。提出了一个校准图，其中将临界胶束浓度与表面活性起始所需浓度作图。在此图中可轻松区分出三个不同区域：极疏水药物区域，这类药物因吸附于膜上而无法进入中枢神经系统；疏水性稍弱的药物中心区域，它们能够穿越血脑屏障；相对亲水药物区域，除非高浓度给药，否则这类药物不会穿越血脑屏障。此图可用于通过简单测量未知化合物的吉布斯吸附等温线，可靠地预测其对中枢神经系统的通透性。
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