The ultimate goal of QSAR analysis focusing on blood-brain barrier penetration is the ability to discriminate between CNS active and inactive molecules. The objective of the current study was to establish the relationship between quantitative blood-brain transport parameters and qualitative data indicating whether the compound penetrates into the brain efficiently enough to exhibit central action. Two quantitative characteristics were considered: brain/plasma equilibration rate, and the extent of brain/plasma partitioning at equilibrium (logBB). Analysis of a diverse data set consisting of >1500 compounds from World Drug Index database with experimentally assigned brain penetration categories revealed that a linear combination of the above mentioned parameters allowed classifying drugs by CNS access with 94% overall accuracy. Furthermore, the devised classification score well correlated with unbound brain/plasma partitioning coefficient (logKp,uu), which is recognized as an unambiguous determinant of brain exposure. The obtained results confirm the validity of the proposed classification approach.

Classification of drugs by CNS access: An insight from quantitative blood-brain transport characteristics

243rd National Meeting (2012)

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