Pharmaceutical Research

, Volume 14, Issue 6, pp 763–766 | Cite as

In Vitro Permeability Across Caco-2 Cells (Colonic) Can Predict In Vivo (Small Intestinal) Absorption in Man—Fact or Myth

  • Shiyin Yee


Purpose. To evaluate and optimize the use of Caco-2 cell monolayers to predict thein vivo absorption of a broad range of compounds in man.

Methods. Caco-2 cells are derived from human adenocarcinoma colon cells and spontaneously differentiate when grown on porous polyethylene terephthalate membranes (PETP) in a 12 well format to form monolayers of polarized cells possessing function similar to intestinal enterocytes. Transport experiments were conducted using 21 day cultured cells in a shaking water bath at 37°C. Radiolabeled mannitol was used to determine monolayer integrity. Apparent permeability coefficient (Papp) was calculated from the appearance of drug in the receiver side.

Results. A strong correlation was observed between in vivo human absorption and in vitro Papp for a variety of compounds (R = 0.95, N = 35). For compounds that are substrates of p-glycoprotein (Pgp), use of a Pgp inhibitor resulted in a better estimate of absorption in humans. The results of this study suggest that the overall ranking of compounds with Papp < 1 × 10−6 cm/sec, between 1−10 × 10−6 cm/ sec, and > 10 × 10−6 cm/sec can be classified as poorly (0−20%), moderately (20−70%) and well (70−100%) absorbed compounds, respectively.

Conclusions. These data suggest that Caco-2 cells developed under the culturing and transport conditions defined herein can be used to predict in vivo human absorption of compounds regardless of transport mechanism, viz., transcellular, paracellular and carrier-mediated.

Caco-2 absorption prediction human P-glycoprotein transport 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    P. Artursson and J. Karlsson. Biochem. Biophys. Res. Com. 175:880–885 (1991)PubMedGoogle Scholar
  2. 2.
    W. Rubas, M. E. M. Cromwell, Z. Shahrokh, J. Villagran, T. N. Nguyen, M. Wellton, T. H. Nguyen, and R. J. Mrsny. J. Pharm. Sci. 85:165–169 (1996)PubMedGoogle Scholar
  3. 3.
    P. Artursson. Crit. Rev. Therap. Drug Carrier Systems. 8:305–330 (1991)Google Scholar
  4. 4.
    A. H. Dantzig and L. Bergin. Biochim. Biophys. Acta 1027:211–217 (1990)PubMedGoogle Scholar
  5. 5.
    H. Lennernas, K. Palm, U. Fagerholm, and P. Artursson. Int. J. Pharm. 127:103–107 (1996)Google Scholar
  6. 6.
    S. Cheong, S. A. Dando, K. M. Soucek, and R. A. Morrison. Pharm. Res. 13:120–123 (1996)PubMedGoogle Scholar
  7. 7.
    M. Hu and R. Borchardt. Pharm. Res. 7:1313–1319 (1990)PubMedGoogle Scholar
  8. 8.
    M. Hu, L. Zheng, J. Chen, L. Liu, Y. Li, A. H. Dantzig, and R. E. Stratford, Jr. J. Drug Target. 3:291–300 (1995)PubMedGoogle Scholar
  9. 9.
    J. N. Cogburn, M. G. Donovan, and C. S. Schasteen. Pharm. Res. 8:210–216 (1991)PubMedGoogle Scholar
  10. 10.
    A. Tsuji, H. Takanaga, I. Tamai, and T. Terasaki. Pharm. Res. 11:30–37 (1994)PubMedGoogle Scholar
  11. 11.
    I. Caro, X. Boulenc, M. Rousset, V. Meunier, M. Bourrie, B. Julian, H. Joyeux, C. Roques, Y. Berger, A. Zweibaum, and G. Fabre. Int. J. Pharm. 116:147–158 (1995)Google Scholar
  12. 12.
    C. Chandler, L. M. Zaccaro, and J. B. Moberly. Gastrointest. Liver Physiol. 27:G1118–1125 (1993)Google Scholar
  13. 13.
    G. Wilson. Eur. J. Drug Metab. Pharmacokin. 15:159–163 (1990)Google Scholar
  14. 14.
    S. Lu, A. W. Gough, W. F. Bobrowski, and B. H. Stewart. J. Pharm. Sci. 85:270–273 (1996)PubMedGoogle Scholar
  15. 15.
    L. Z. Benet and R. L. Williams. In A. G. Gilman, T. W. Rall, A. S. Miles, P. Taylor (eds.), The Pharmacological Basis of Therapeutics (eighth edition) Pergamon Press, Elmsford, NY, pp. 1650–1736 (1990)Google Scholar

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • Shiyin Yee
    • 1
  1. 1.Pfizer Inc., Central ResearchGroton

Personalised recommendations