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Journal of Biomolecular Screening, Vol. 9, No. 7, 598-606 (2004)
DOI: 10.1177/1087057104267162

Comparison of in Vitro Models for the Prediction of Compound Absorption across the Human Intestinal Mucosa

Silvia Miret

Unilever R&D Vlaardingen, Unilever Health Institute, Olivier van Hoortlaan, 120, 3133 AC Vlaardingen, the NetherlandsSilvia.miret-catalan{at}unilever.com

Leo Abrahamse

Els M. de Groene

Several in vitro assays have been developed to evaluate the gastrointestinal absorption of compounds. Our aim was to compare 3 of these methods: 1) the bio-mimetic artificial membrane permeability assay (BAMPA) method, which offers a high-throughput, noncellular approach to the measurement of passive transport; 2) the traditional Caco-2 cell assay, the use of which as a high-throughput tool is limited by the long cell differentiation time (21 days); and 3) The BioCoatTM high-throughput screening Caco-2 Assay System, which reduces Caco-2 cell differentiation to 3 days. The transport of known compounds (such as cephalexin, propranolol, or chlorothiazide) was studied at pH 7.4 and 6.5 in BAMPA and both Caco-2 cell models. Permeability data obtained was correlated to known values of human absorption. Best correlations (r = 0.9) were obtained at pH 6.5 for BAMPA and at pH 7.4 for the Caco-2 cells grown for 21 days. The Caco-2 BioCoatTM HTS Caco-2 Assay System does not seem to be adequate for the prediction of absorption. The overall results indicate that BAMPA and the 21-day Caco-2 system can be complementary for an accurate prediction of human intestinal absorption.

Key Words: BAMPA • bioavailability • Caco-2 • permeability


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