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Journal of Biomolecular Screening
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Paraben Transport and Metabolism in the Biomimetic Artificial Membrane Permeability Assay (BAMPA) and 3-Day and 21-Day Caco-2 Cell Systems

Mark Lakeram

King's College London, Pharmaceutical Science Research Division, London, UK

David J. Lockley

David J. Sanders

Ruth Pendlington

Safety and Environmental Assurance Centre, Unilever Colworth, Sharnbrook, Bedfordshire, UK

Ben Forbes

King's College London, Pharmaceutical Science Research Division, London, UK

Noncellular and cellular in vitro models for predicting intestinal absorption were used to investigate the transport and metabolism of parabens. The biomimetic artificial membrane permeability assay (BAMPA) membrane was constructed by impregnating a lipid solution on a hydrophobic filter. Caco-2 cells at passage numbers 65 to 80 were cultured in either the accelerated 3-day BiocoatTM system or the standard 21-day TranswellTM cell culture system. Paraben transport across the BAMPA system showed a parabolic relationship. The lowest log P (p-hydroxybenzoic acid) and highest log P compounds (heptyl and octyl parabens) had apparent permeabilities (Papp) less than 1.0 x 10-6 cm/s and Papp was maximal at approximately 8.5 x 10-6cm/s for the intermediate log P (ethylparaben) compound. With the BiocoatTM, a similar parabolic relationship was found. In the 21-day Caco-2 cells, the parabens were metabolized by esterases at to p-hydroxybenzoic acid. In conclusion, the in vitro models added complementary insight into the absorption process, such as the transport route, intrinsic permeability, and extent of metabolism of the parabens. This study indicated that presystemic metabolism of orally ingested parabens to the p-hydroxybenzoic acid in the intestine may limit systemic exposure to alkyl-paraben esters in vivo.

Key Words: BAMPA • BiocoatTM • Caco-2cells • intestinal metabolism • parabens

This version was published on February 1, 2007

Journal of Biomolecular Screening, Vol. 12, No. 1, 84-91 (2007)
DOI: 10.1177/1087057106295383
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