Physicochemical properties and transport of steroids across Caco-2 cells.
OBJECTIVE
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.
Faassen
Fried
F
Department of Pharmaceutics, NV Organon, P.O. Box 20, 5340 BH Os, The Netherlands. fried.faassen@organon.com
Kelder
Jan
J
Lenders
Johan
J
Onderwater
Rob
R
Vromans
Herman
H
D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D012995:Solubility; D013256:Steroids / Q000737:chemistry* / Q000493:pharmacokinetics*
D013256:Steroids