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The "latent membrane permeability" concept: QSPR analysis of inter/intralaboratory variable Caco-2 permeability
Fumiyoshi Yamashita1, Shin-ichi Fujiwara, Mitsuru Hashida
1Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Abstract:
Caco-2 cell monolayers grown on a filter support are the most widely used systems for predicting intestinal absorption. However, inter- and intralaboratory variability in Caco-2 permeability makes it difficult to analyze any QSPR relationship for a large number of compounds. We proposed the "latent membrane permeability" concept, assuming that all Caco-2 permeability data sets share a hidden, common relationship between their membrane permeability and physicochemical properties. An iterative calculation method was developed to handle this conceptual approach and applied to the analysis of Caco-2 permeability data sets from different sources. A thorough statistical analysis revealed that the "latent membrane permeability" concept be reasonable.