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Use of simulated intestinal fluid for Caco-2 permeability assay of lipophilic drugs.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2008 Aug 06; Vol. 360 (1-2), pp. 148-55. Date of Electronic Publication: 2008 Apr 29. - Publication Year :
- 2008
-
Abstract
- The most commonly used method to assess intestinal permeability is the measurement of compound flux across a Caco-2 cells monolayer by using Hanks balanced salt solution (HBSS)-like buffers. Nevertheless, lipophilic acid drugs are poorly or not at all soluble in these types of buffers and their adsorption on the transwell plate is commonly observed. To reduce adsorption and increase solubility, permeability assays need to be developed in conditions other than classic conditions for lipophilic compounds. The best model to increase recovery of lipophilic compounds was determined as fasted state simulated intestinal fluid (FaSSIF) in the apical compartment and HBSS with 1% bovine serum albumin (BSA) in basolateral compartment. This model allows a correlation between absorption on Caco-2 cells and absorbed fraction in humans. For 35 compounds, only 2 outliers were observed in the Caco-2 assay using the FaSSIF model. These two outliers were the same outlier compounds as those observed with a classic Caco-2 method. Furthermore, a permeability assay of Pgp substrates evidenced efflux transport in both models and addition of a Pgp inhibitor suppressed Pgp efflux transport. FaSSIF in the apical compartment and HBSS with 1% BSA in the basolateral compartment is the model of choice to predict in vivo absorption for lipophilic acid drugs.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B, Member 1 antagonists & inhibitors
ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism
Biological Transport, Active drug effects
Buffers
Caco-2 Cells
Cell Membrane Permeability drug effects
Chromatography, High Pressure Liquid
Humans
Intestinal Absorption drug effects
Mass Spectrometry
Cell Membrane Permeability physiology
Intestinal Absorption physiology
Pharmaceutical Preparations metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0378-5173
- Volume :
- 360
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 18539418
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2008.04.034