, Volume 14, Issue 6, pp 763-766

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

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Abstract

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.