Cell Culture Models with In Vivo Brain Penetration

Correlation of Cell Culture Models with In Vivo Brain Penetration 

There are a number of in vivo methods used to assess brain penetration each with their own benefits and limitations [41]. Much of the in vivo data comes from the brain blood ratio, which is not a direct measure of permeability and therefore is not directly comparable to in vitro permeability values [4]. 

Recently Carrara et al. looked at the utility of optimized PAMPA and MDCK-MDRl cells in predicting brain penetration for known CNS-penetratrng and nonpenetrating drugs. The MDCK-MDRl cells correctly predicted 29 out of the 34 compounds (85%) which had known CNS penetration [42[. 

Garberg et al. compared a number of in vitro cell models of the BBB with in vivo data (including primary cow and human brain endothelial cells co-cultured with astrocytes, MDCK, MDCK-MDRl, Caco-2, ECV304/C6, MBEC4, SV-ARBEC cocultured with astrocytes). The best correlation, although poor, was seen with cow brain endothelial cells (r 0.43) and MDCK (r 0.46). The correlation was improved with Caco-2 when only passively transported compounds were included in the analysis (r = 0.86), BBEC showing a similar correlation [39]. 

Eurther understanding of active transporters in the brain and in in vitro models is required to improve predictability of these models. 

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