On the rate and extent of drug delivery to the brain.
On the rate and extent of drug delivery to the brain.
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关于药物输送到大脑的速度和程度。
DOI：
10.1007/s11095-007-9502-2
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发表时间：
2008-08
影响因子：
3.7
通讯作者：
Gupta, Anubha
中科院分区：
文献类型：
--
作者：
Hammarlund-Udenaes, Margareta;Friden, Markus;Syvanen, Stina;Gupta, Anubha
定义和区分血脑屏障转运和分布的相关方面，以帮助脑药物递送的研究方法。药代动力学参数相对于大脑药物输送的速度和程度的描述和说明与相关数据，特别强调的是未结合的，非活性药物分子。可以使用三个参数全面描述药物向脑的递送：Kp，uu（脑中未结合药物与血液的浓度比）、CLin（进入脑的渗透性清除率）和Vu，brain（脑内分布）。血脑屏障的渗透性与药物在中枢神经系统内的作用的相关性不如药物递送的程度，因为大多数药物是连续（重复）给药的。Kp，uu在CNS活性药物之间的差异高达150倍。该范围远小于对数BB比率（Kp）的范围，对数BB比率（Kp）的范围可以相差高达至少2，000倍，或者BBB渗透性的范围甚至更大（相差高达至少20，000倍）。测量三个参数Kp，uu，CLin和Vu，brain的方法可以在早期药物发现计划中对脑药物递送进行有临床价值的估计。
To define and differentiate relevant aspects of blood–brain barrier transport and distribution in order to aid research methodology in brain drug delivery. Pharmacokinetic parameters relative to the rate and extent of brain drug delivery are described and illustrated with relevant data, with special emphasis on the unbound, pharmacologically active drug molecule. Drug delivery to the brain can be comprehensively described using three parameters: Kp,uu (concentration ratio of unbound drug in brain to blood), CLin (permeability clearance into the brain), and Vu,brain (intra-brain distribution). The permeability of the blood–brain barrier is less relevant to drug action within the CNS than the extent of drug delivery, as most drugs are administered on a continuous (repeated) basis. Kp,uu can differ between CNS-active drugs by a factor of up to 150-fold. This range is much smaller than that for log BB ratios (Kp), which can differ by up to at least 2,000-fold, or for BBB permeabilities, which span an even larger range (up to at least 20,000-fold difference). Methods that measure the three parameters Kp,uu, CLin, and Vu,brain can give clinically valuable estimates of brain drug delivery in early drug discovery programmes.
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影响因子：
7.3
作者：
Bouw, MR;Xie, RJ;Hammarlund-Udenaes, M
通讯作者：
Hammarlund-Udenaes, M
影响因子：
3.7
作者：
Bouw, MR;Gårdmark, M;Hammarlund-Udenaes, M
通讯作者：
Hammarlund-Udenaes, M
影响因子：
5.8
作者：
Dagenais, C;Graff, CL;Pollack, GM
通讯作者：
Pollack, GM
影响因子：
3.1
作者：
Carson, RE
通讯作者：
Carson, RE
影响因子：
3.9
作者：
Becker, S;Liu, XR
通讯作者：
Liu, XR