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71 PERMEABILITY IN THE GASTROINTESTINAL TRACT AND AT THE BLOOD BRAIN BARRIER Measured permeability (especially when combined with solubility and charge state) can be viewed as a surrogate property for predicting oral (gastrointestinal) absorption of preclinical drug candidate molecules This chapter considers the transport of molecules by passive diffusion through phospholipid bilayers The emphasis is on (1) the current state-of-the-art measurement of permeabilities by the so-called PAMPA method and (2) the theoretical physicochemical models that attempt to rationalize the observed transport properties Such models are expected to lead to new insights into the in vivo absorption processes In oral absorption predictions, the established in vitro assay to assess the permeability coef cients is based on Caco-2 cultured-cell con uent monolayers [48,510 515] We refer to this topic in various places, drawing on the biophysical aspects of the work reported in the literature We also consider some physicochemical properties of the blood brain barrier (BBB), insofar as they contrast to those of the gastrointestinal tract (GIT) Our main focus, however, is on results derived from simpler in vitro systems based on arti cial membranes In order to rationalize membrane permeability and oral absorption in terms of physicochemical drug properties, good experimental data and sound theoretical

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Absorption and Drug Development: Solubility, Permeability, and Charge State By Alex Avdeef ISBN 0-471-423653 Copyright # 2003 John Wiley & Sons, Inc

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