Prediction of in situ Blood-Brain Barrier Permeability using BBB PAMPA Model

Purpose.  This study was conducted to assess the permeability of the blood-brain barrier (BBB) to drug-like compounds with a wide range of molecular properties, using the in situ brain perfusion technique in P-glycoprotein (Pgp) deficient [mdr1a(-/-)] mice, and to predict this permeability using an in combo PAMPA (in silico supported parallel artificial membrane permeability assay) model.

Conclusion.  The in situ brain perfusion measurements of drug-like molecules, in Pgp deficient mice, can be predicted by an in combo PAMPA method to a satisfactory degree, based on a training set of in situ BBB measurements.  The speed of the PAMPA method, and its substantial lower cost, compared to in vivo measurements, make it an attractive first-pass screening method for BBB passive permeability.