A linear free energy analysis of PAMPA models for biological systems

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Abstract

Equation coefficients in the Abraham linear free energy relationship have been obtained for a number of parallel artificial membrane permeability assays, PAMPA, and have been compared to equation coefficients for several biological processes and a large number of water-solvent partitions. From a principal component analysis of the equation coefficients we show that one particular PAMPA (Wohnsland and Faller, 2001) is a good model for human intestinal absorption, but we could find no PAMPA that was a good model for rat brain permeation, mouse brain permeation, blood–brain distribution, skin permeation or water–skin partition, although models that include PAMPA and other descriptors may be useful. The water–octanol system is a poor model for all the biological process we have studied, but water-nonpolar solvent partitions are good models for permeation through egg lecithin membranes.

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