Title
Physicochemical properties and transport of steroids across Caco-2 cells
Author
Faassen, F.
Kelder, J.
Lenders, J.
Onderwater, R.
Vromans, H.
Publication year
2003
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.
Subject
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
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http://resolver.tudelft.nl/uuid:b7ebc030-bcff-44b8-8689-484c0397a2c8
DOI
https://doi.org/10.1023/a:1022210801734
TNO identifier
236955
ISSN
0724-8741
Source
Pharmaceutical Research, 20 (2), 177-186
Document type
article