Get access

Variability in Caco-2 and MDCK cell-based intestinal permeability assays

Authors

  • Donna A. Volpe

    Corresponding author
    1. Division of Product Quality Research, Life Sciences Bldg. 64, 10903 New Hampshire Ave., Silver Spring, Maryland 20993-0002
    • Division of Product Quality Research, Life Sciences Bldg. 64, 10903 New Hampshire Ave., Silver Spring, Maryland 20993-0002. Telephone: 301-796-0014; Fax: 301-796-9816
    Search for more papers by this author

  • This article represents the personal opinions of the author and does not necessarily reflect the views or policies of the FDA.

Abstract

Models predictive of intestinal drug absorption are important in drug development to identify compounds with promising biopharmaceutical properties. Since permeability is a factor affecting absorption, cell culture models (e.g., Caco-2, MDCK) have been developed to predict drug transport from the intestinal lumen into the bloodstream. The differences as to how the assays are performed, along with heterogeneity of the cell lines, have lead to different permeability values for the same drug. Transport and metabolic properties of cultured cells can vary due to culture conditions, seeding density, passage number, confluency, filter support, monolayer age, and stage of differentiation. During the transport experiment, cell absorption properties can change due to the composition and pH of the transport buffer, solute concentration and solubility, temperature, additives and/or cosolvents, agitation, sampling schedule, sink conditions, and analytical methods. Such variability within a laboratory can be avoided by characterizing a cell culture method and setting acceptance criteria in terms of monolayer integrity, passive transport, and active transport. The repeated evaluation of reference compounds will then facilitate intra-laboratory comparisons. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:712–725, 2008

Get access to the full text of this article

Ancillary