Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/111908
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dc.contributor.authorDahley, Carolin-
dc.contributor.authorGoss, Kai-Uwe-
dc.contributor.authorEbert, Andrea-
dc.date.accessioned2023-11-22T07:44:03Z-
dc.date.available2023-11-22T07:44:03Z-
dc.date.issued2023-
dc.identifier.urihttps://opendata.uni-halle.de//handle/1981185920/113866-
dc.identifier.urihttp://dx.doi.org/10.25673/111908-
dc.description.abstractIntrinsic membrane permeability is one of several factors that critically determine the intestinal absorption of a chemical. The intrinsic membrane permeability of a chemical is usually extracted from transwell experiments with Caco-2 or MDCK cells, preferably by the pKa-Flux method, which is considered the method of choice when aqueous boundary layer effects need to be excluded. The pKa-Flux method has two variants, the iso-pH method, where apical and basolateral pH are equal, and the gradient-pH method, where apical and basolateral pH are different. The most commonly used method is the gradient-pH method, as it is intended to reflect the pH-conditions in the gastrointestinal tract. However, concentration-shift effects caused by the applied pH-difference between apical and basolateral compartment in the gradient-pH method have not been considered in the evaluation of the experimental data in the past. Consequently, incorrect intrinsic membrane permeabilities have been determined. In this work, we present a revised method for extracting the intrinsic membrane permeability from gradient-pH data that considers concentration-shift effects in the basolateral aqueous boundary layer and filter as well as in the cytosol. Furthermore, we propose the use of the iso-pH method, where only concentration-shift effects in the cytosol need to be considered, as an alternative to the gradient-pH method. We use the five lipophilic bases amantadine, chloroquine, propranolol, venlafaxine and verapamil as examples to compare gradient-pH method and iso-pH method with regard to the extractability of the intrinsic membrane permeability. For lipophilic bases, the iso-pH method proves to be advantageous. All intrinsic membrane permeabilities determined in this work were substantially higher than the intrinsic membrane permeabilities reported in literature.eng
dc.language.isoeng-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subject.ddc540-
dc.titleRevisiting the pKa-Flux method for determining intrinsic membrane permeabilityeng
dc.typeArticle-
local.versionTypepublishedVersion-
local.bibliographicCitation.journaltitleEuropean journal of pharmaceutical sciences-
local.bibliographicCitation.volume191-
local.bibliographicCitation.publishernameElsevier-
local.bibliographicCitation.publisherplaceNew York, NY [u.a.]-
local.bibliographicCitation.doi10.1016/j.ejps.2023.106592-
local.subject.keywordspKa-Flux method, Passive permeability, Aqueous boundary layer, Concentration-shift, MDCK, Caco-2-
local.openaccesstrue-
dc.identifier.ppn1870845323-
cbs.publication.displayform2023-
local.bibliographicCitation.year2023-
cbs.sru.importDate2023-11-22T07:43:43Z-
local.bibliographicCitationEnthalten in European journal of pharmaceutical sciences - New York, NY [u.a.] : Elsevier, 1993-
local.accessrights.dnbfree-
Appears in Collections:Open Access Publikationen der MLU

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