alexa In vitro trans-monolayer permeability calculations: often forgotten assumptions.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Youdim KA, Avdeef A, Abbott NJ

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Abstract In designing effective therapeutic strategies, novel drugs must exhibit favorable pharmacokinetic properties. The physicochemical characteristics of a drug, such as pK(a), molecular weight, solubility and lipophilicity, will influence the way the drug partitions from the aqueous phase into membranes, and thus, will influence its ability to cross cellular barriers, such as the lining of the gastrointestinal tract and the blood-brain barrier. Physicochemical characteristics also influence the degree to which a drug is able to cross a barrier layer, and the route by which it does this; whether transcellular (across the cells)-by diffusion, carrier-mediated transport or transcytosis-or paracellular-by diffusing through the tight junctions between the cells. The in vitro model systems that are currently employed to screen the permeation characteristics of a drug often represent a compromise between high throughput with low predictive potential and low throughput with high predictive potential. Here, we will examine the way in which in vitro cellular permeability assays are often performed and the assumptions that are implied but sometimes forgotten, and we will make simple suggestions for improving the methodological techniques and mathematical equations used to determine drug permeability.
This article was published in Drug Discov Today and referenced in Journal of Bioequivalence & Bioavailability

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