In situ artificial membrane permeation assay under hydrodynamic control: Correlation between drug in vitro permeability and fraction absorbed in humansCitation formats

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In situ artificial membrane permeation assay under hydrodynamic control: Correlation between drug in vitro permeability and fraction absorbed in humans. / Velický, Matěj; Tam, Kin Y.; Dryfe, Robert A W.

In: European Journal of Pharmaceutical Sciences, Vol. 44, No. 3, 09.10.2011, p. 299-309.

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@article{f53f2dc42d284c4c9a2efbfae868f809,
title = "In situ artificial membrane permeation assay under hydrodynamic control: Correlation between drug in vitro permeability and fraction absorbed in humans",
abstract = "The purpose of this study was to develop an in vitro permeation model that will predict the fraction of drugs absorbed in humans. A rotating-diffusion cell with two aqueous compartments, separated by a lipid-impregnated artificial membrane, was used to determine the permeability of drugs under conditions of controlled hydrodynamics. The measured effective permeability coefficient was modified to include the paracellular transport derived from a previously reported colorectal adenocarcinoma epithelial cell line (Caco-2) permeability study and the effects of unstirred water layer anticipated in vivo. Permeability data were collected for 31 different marketed drugs with known absolute oral bioavailability and human hepatic clearance data. Literature bioavailability values were corrected for the first pass hepatic clearance thus obtaining the fraction absorbed from intestinal lumen (fraction absorbed), F a, while assuming that the fraction escaping intestinal extraction, F g, was approximately ∼1. Permeability obtained under conditions of controlled hydrodynamics was compared with the permeability measured under unstirred conditions. It is shown that the optimized effective permeability correlates with the fraction absorbed. In contrast, permeability data obtained under unstirred conditions does not show a good correlation. The in vitro permeation model developed in this study predicts the fraction absorbed of the selected drugs in humans within experimental uncertainty. It has been demonstrated that the correlation with the fraction absorbed is greatly improved using the permeability data obtained under controlled hydrodynamics with paracellular transport included in the model. {\circledC} 2011 Elsevier B.V. All rights reserved.",
keywords = "Drug absorption, In situ permeation, PAMPA, Paracellular transport, Stirring, Unstirred water layer",
author = "Matěj Velick{\'y} and Tam, {Kin Y.} and Dryfe, {Robert A W}",
year = "2011",
month = "10",
day = "9",
doi = "10.1016/j.ejps.2011.08.007",
language = "English",
volume = "44",
pages = "299--309",
journal = "European Journal of Pharmaceutical Sciences",
issn = "0928-0987",
publisher = "Elsevier BV",
number = "3",

}

RIS

TY - JOUR

T1 - In situ artificial membrane permeation assay under hydrodynamic control: Correlation between drug in vitro permeability and fraction absorbed in humans

AU - Velický, Matěj

AU - Tam, Kin Y.

AU - Dryfe, Robert A W

PY - 2011/10/9

Y1 - 2011/10/9

N2 - The purpose of this study was to develop an in vitro permeation model that will predict the fraction of drugs absorbed in humans. A rotating-diffusion cell with two aqueous compartments, separated by a lipid-impregnated artificial membrane, was used to determine the permeability of drugs under conditions of controlled hydrodynamics. The measured effective permeability coefficient was modified to include the paracellular transport derived from a previously reported colorectal adenocarcinoma epithelial cell line (Caco-2) permeability study and the effects of unstirred water layer anticipated in vivo. Permeability data were collected for 31 different marketed drugs with known absolute oral bioavailability and human hepatic clearance data. Literature bioavailability values were corrected for the first pass hepatic clearance thus obtaining the fraction absorbed from intestinal lumen (fraction absorbed), F a, while assuming that the fraction escaping intestinal extraction, F g, was approximately ∼1. Permeability obtained under conditions of controlled hydrodynamics was compared with the permeability measured under unstirred conditions. It is shown that the optimized effective permeability correlates with the fraction absorbed. In contrast, permeability data obtained under unstirred conditions does not show a good correlation. The in vitro permeation model developed in this study predicts the fraction absorbed of the selected drugs in humans within experimental uncertainty. It has been demonstrated that the correlation with the fraction absorbed is greatly improved using the permeability data obtained under controlled hydrodynamics with paracellular transport included in the model. © 2011 Elsevier B.V. All rights reserved.

AB - The purpose of this study was to develop an in vitro permeation model that will predict the fraction of drugs absorbed in humans. A rotating-diffusion cell with two aqueous compartments, separated by a lipid-impregnated artificial membrane, was used to determine the permeability of drugs under conditions of controlled hydrodynamics. The measured effective permeability coefficient was modified to include the paracellular transport derived from a previously reported colorectal adenocarcinoma epithelial cell line (Caco-2) permeability study and the effects of unstirred water layer anticipated in vivo. Permeability data were collected for 31 different marketed drugs with known absolute oral bioavailability and human hepatic clearance data. Literature bioavailability values were corrected for the first pass hepatic clearance thus obtaining the fraction absorbed from intestinal lumen (fraction absorbed), F a, while assuming that the fraction escaping intestinal extraction, F g, was approximately ∼1. Permeability obtained under conditions of controlled hydrodynamics was compared with the permeability measured under unstirred conditions. It is shown that the optimized effective permeability correlates with the fraction absorbed. In contrast, permeability data obtained under unstirred conditions does not show a good correlation. The in vitro permeation model developed in this study predicts the fraction absorbed of the selected drugs in humans within experimental uncertainty. It has been demonstrated that the correlation with the fraction absorbed is greatly improved using the permeability data obtained under controlled hydrodynamics with paracellular transport included in the model. © 2011 Elsevier B.V. All rights reserved.

KW - Drug absorption

KW - In situ permeation

KW - PAMPA

KW - Paracellular transport

KW - Stirring

KW - Unstirred water layer

U2 - 10.1016/j.ejps.2011.08.007

DO - 10.1016/j.ejps.2011.08.007

M3 - Article

VL - 44

SP - 299

EP - 309

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

SN - 0928-0987

IS - 3

ER -