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PAMPA study of the temperature effect on permeability. | LitMetric
The purpose of this work was to investigate the temperature dependence of permeability measured by PAMPA method. The effective permeability (logPe) of seven drugs representing diverse structures and different acid-base properties was determined on three membrane models (GIT, BBB, Skin). The incubation temperature was varied in the range of 15-55 °C with ten degree steps. The intrinsic permeability (logP0) of the compounds is in linear relation with temperature (T). The slope of the logP0=aT+b regression equation is a good measure of the temperature effect on permeability. Results show intensive and significant temperature dependence of permeability influenced by the properties of the compounds and also by the selected PAMPA model. The Skin PAMPA(™) proved to be the most sensitive on temperature alteration, though GIT and BBB PAMPA results were also affected. The compound with acid function showed the lowest temperature dependence, while the permeability of bases increased considerably in response to the increasing temperature. The importance of human-relevant incubation conditions at in vitro assays is concluded for the better in vivo prediction.
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