Utility of CSF in translational neuroscience.
Utility of CSF in translational neuroscience.
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DOI：
10.1007/s10928-013-9301-9
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发表时间：
2013-06
影响因子：
2.5
通讯作者：
de Lange, Elizabeth C. M.
中科院分区：
文献类型：
--
作者：
de Lange, Elizabeth C. M.
关键词：
人脑脊液（CSF）采样作为获得个体人脑中游离药物浓度信息的唯一通用方法具有很高的价值。由于最终关注的是CNS靶位点的游离药物浓度，因此问题是CSF浓度在这方面可以告诉我们什么。在大鼠和其他动物中进行了研究，在假定的稳态条件下，将脑细胞外液（脑ECF）中的浓度（作为许多药物的靶点）与（小脑延髓池）CSF浓度进行了比较。数据表明，CSF药物浓度提供了一个相当好的指示，但不是一个可靠的措施，用于预测脑ECF浓度。此外，将大鼠CSF浓度与人CSF浓度进行比较，人CSF浓度往往更高，并显示出更大的变异性。然而，这种CSF浓度的比较不能是直接的，因为人类可能患有某种疾病，首先收集CSF，而大鼠是健康的。为了能够更准确地预测人脑ECF浓度，需要增加对CNS在脑内药代动力学关系方面的复杂性以及CNS疾病对脑药代动力学的影响的理解。这可以通过扩展目前现有的临床前衍生的基于生理学的脑分布药代动力学模型来实现。该模型已被证明可以成功预测对乙酰氨基酚的人腰椎CSF浓度的数据，这使得对人脑ECF浓度的模型预测具有可信度。该模型应通过纳入药物性质、液体流动、转运蛋白功能和不同疾病状况的影响来进一步发展。最后，该模型应包括靶位点参与和CNS效应的测量，以最终通过人CSF浓度了解最佳预测特定靶位点浓度的浓度。
Human cerebrospinal fluid (CSF) sampling is of high value as the only general applicable methodology to obtain information on free drug concentrations in individual human brain. As the ultimate interest is in the free drug concentration at the CNS target site, the question is what CSF concentrations may tell us in that respect. Studies have been performed in rats and other animals for which concentrations in brain extracellular fluid (brain ECF) as a target site for many drugs, have been compared to (cisterna magna) CSF concentrations, at presumed steady state conditions,. The data indicated that CSF drug concentrations provided a rather good indication of, but not a reliable measure for predicting brain ECF concentrations. Furthermore, comparing rat with human CSF concentrations, human CSF concentrations tend to be higher and display much more variability. However, this comparison of CSF concentrations cannot be a direct one, as humans probably had a disease for which CSF was collected in the first place, while the rats were healthy. In order to be able to more accurately predict human brain ECF concentrations, understanding of the complexity of the CNS in terms of intrabrain pharmacokinetic relationships and the influence of CNS disorders on brain pharmacokinetics needs to be increased. This can be achieved by expanding a currently existing preclinically derived physiologically based pharmacokinetic model for brain distribution. This model has been shown to successfully predict data obtained for human lumbar CSF concentrations of acetaminophen which renders trust in the model prediction of human brain ECF concentrations. This model should further evolute by inclusion of influences of drug properties, fluid flows, transporter functionalities and different disease conditions. Finally the model should include measures of target site engagement and CNS effects, to ultimately learn about concentrations that best predict particular target site concentrations, via human CSF concentrations.
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影响因子：
2.1
作者：
Bouw, R;Ederoth, P;Hammarlund-Udenaes, M
通讯作者：
Hammarlund-Udenaes, M
影响因子：
7.3
作者：
Friden, Markus;Winiwarter, Susanne;Antonsson, Madeleine
通讯作者：
Antonsson, Madeleine
DOI：
10.1111/j.1365-2125.1992.tb04112.x
发表时间：
1992-07-01
影响因子：
3.4
作者：
BANNWARTH, B;NETTER, P;GAUCHER, A
通讯作者：
GAUCHER, A
影响因子：
5.8
作者：
BRUCE, J;TAMARKIN, L;OLDFIELD, E
通讯作者：
OLDFIELD, E
影响因子：
3.9
作者：
Au-Yeung, Sam C. S.;Rurak, Dan W.;Riggs, K. Wayne
通讯作者：
Riggs, K. Wayne