Evaluation of in vitro brain penetration:: Optimized PAMPA and MDCKII-MDR1 assay comparison
Evaluation of in vitro brain penetration:: Optimized PAMPA and MDCKII-MDR1 assay comparison
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DOI：
10.1016/j.ijpharm.2007.05.057
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发表时间：
2007-12-10
影响因子：
5.8
通讯作者：
Bigogno, Chiara
中科院分区：
文献类型：
--
作者：
Carrara, Simone;Reali, Veronica;Bigogno, Chiara
平行人工膜渗透试验（PAMPA）是在ADMET筛选中出现的，作为一种强有力的工具来确定新的潜在化学实体的被动渗透性。为了建立一种灵敏的高通量方法来评价PAMPA对血脑屏障（BBB）的被动渗透，我们着重研究了溶剂和磷脂对PAMPA渗透性的影响。此外，通过减少孵育时间并以试剂卡模式进行测定，使测定的高通量性质最大化。UPLC系统与质谱仪联用极大地缩短了分析时间，同时提高了方法的灵敏度。将从PAMPA获得的P-app值与从MDCKII-MDR 1测定获得的渗透率值进行比较。用体内数据对两种体外模型进行评价，以检验两种方法的预测能力。他们的当代评估被证明是一个有用的工具，在了解通过血脑屏障渗透的普遍机制。(c)2007 Elsevier B. V.保留所有权利。
Parallel artificial membrane permeability assay (PAMPA) is arising in ADMET screening as a powerful tool to determine the passive permeability of new potential chemical entities. In an attempt to set up a sensitive high throughput method to assess passive blood-brain barrier (BBB) penetration we focused our attention on the effect of solvent and the influence of phospholipids on the permeability in PAMPA. Moreover, the high throughput nature of the assay was maximized by decreasing the incubation time and performing the assay in a cassette mode. UPLC system coupled with a mass spectrometer enormously reduces the analytical time, contemporaneously increasing the sensitivity of the method.P-app values obtained from PAMPA were compared to permeability values from MDCKII-MDR1 assay. Evaluation of the two in vitro models with in vivo data was performed to test the predicting capacity of the two methods. Their contemporary assessment was shown to be an helpful tool in understanding the prevalent mechanism of penetration through the BBB. (c) 2007 Elsevier B.V. All rights reserved.