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Physicochemical properties and transport of steroids across Caco-2 cells

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Author: Faassen, F. · Kelder, J. · Lenders, J. · Onderwater, R. · Vromans, H.
Type:article
Date:2003
Source:Pharmaceutical Research, 2, 20, 177-186
Identifier: 236955
doi: doi:10.1023/A:1022210801734
Keywords: Drugs · Physiological Sciences · Absorption · Caco-2 permeability · Physicochemical properties · Steroids · 17alpha hydroxy 11 methylene 19 norpregna 4,15 dien 20 yn 3 one · aldosterone · cefalexin · cortisone · dexamethasone · estradiol · ethinylestradiol · etonogestrel · gestodene · glucose · hydrocortisone · macrogol 4000 · mannitol · nandrolone · norethisterone · norgestrel · org 32540 · org 34694 · org 36410 · org 4060 · org 4325 · org om 08 · phenazone · prednisolone · progesterone · spironolactone · steroid · testosterone · verapamil · article · calculation · cell membrane permeability · cell strain CACO 2 · controlled study · drug absorption · drug surveillance program · drug transport · human · human cell · molecular weight · physical chemistry · priority journal · Biological Transport · Caco-2 Cells · Chemistry, Physical · Humans · Solubility · Steroids

Abstract

Purpose. The purpose of this work was to study the relevant physicochemical properties for the absorption of steroids. Methods. Various physicochemical properties of steroids were calculated (molecular weight, ClogP, static polar surface area [PSA], etc.). Within this series of steroids, different pharmacological groups were defined. Based on the outcome of this survey, steroids were selected for the Caco-2 permeability study. The apparent permeability coefficients (Papp) were related to the calculated and measured physicochemical properties. Results. Between the defined groups of steroids, ClogP was the most discriminative descriptor. The steroids were well transported over the cell monolayers and the Papp was independent of the concentration and the transport direction. No relationship was found with the PSA; however, the Papp showed a weak inverse correlation with ClogP. Conclusions. The molecular descriptors and Papp values showed that all steroids are well transported. The small differences in the Papp values showed a weak inverse correlation with ClogP: the hydrophilic steroids (ClogP approximately 0-2) tend to diffuse faster over the cell monolayers compared with the more hydrophobic steroids (ClogP approximately 5). The relationship with ClogP suggests that partitioning of steroids between the biologic membrane and the surrounding aqueous phase is one of the main mechanisms for absorption.