Title: Evaluation of fasted state human intestinal fluid as apical solvent system in the Caco-2 absorption model and comparison with FaSSIF
Authors: Wuyts, Ben ×
Riethorst, Danny
Brouwers, Joachim
Tack, Jan
Annaert, Pieter
Augustijns, Patrick #
Issue Date: Jan-2015
Publisher: Elsevier
Series Title: European Journal of Pharmaceutical Sciences vol:67 pages:126-35
Abstract: To date, the Caco-2 model is considered as the gold standard to predict intestinal drug absorption. Often, aqueous phosphate buffers are used as apical medium. The purpose of this study was to use fasted state human intestinal fluid (FaHIF) as apical solvent system to generate biorelevant permeability values for a series of 16 model drugs that can be used as reference data to critically evaluate fasted state simulated intestinal fluid (FaSSIF) as possible substitute medium. Caco-2 compatibility with FaHIF was achieved when 50mg/ml mucus was applied on top of the cells before adding the apical medium. The use of FaHIF as solvent system generated a broad range of apparent permeability values (Papp) for the series of model compounds. When Papp values obtained with FaHIF were compared to those obtained with FaSSIF, a strong correlation was observed (R=0.951). The use of FaSSIF in the absence of mucus did not significantly alter this correlation. For FaHIF, FaSSIF and reference phosphate buffer blank FaSSIF, a strong sigmoidal relationship was found between Papp and fahuman, illustrated by correlation coefficients of 0.961, 0.893 and 0.868, respectively. In terms of inter-subject variability, the use of FaHIF from different volunteers originating from two distinct age groups (18-25years; 65-72years) exhibited an average coefficient of variance (CV) of 30%. However, no age dependency in permeability could be observed. In conclusion, the data generated in this article justify the use of FaSSIF as biorelevant apical medium in the Caco-2 assay to accurately predict in vivo drug absorption. Also, the optimized mucus-containing Caco-2 model can be used in combination with intestinal fluid samples aspirated after drug administration to further investigate intraluminal drug and formulation behavior.
ISSN: 0928-0987
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
Field of Study Social and Community Work Odisee
Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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