caa a22 4500 477125859 CHVBK 20180405111649.0 cr unu---uuuuu 170330e19970601xx s 000 0 eng 10.1023/A:1012102522787 doi (NATIONALLICENCE)springer-10.1023/A:1012102522787 Yee Shiyin Pfizer Inc., Central Research, Eastern Point Rd., 06340, Groton, Connecticut aut In Vitro Permeability Across Caco-2 Cells (Colonic) Can Predict In Vivo (Small Intestinal) Absorption in Man—Fact or Myth [Elektronische Daten] [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. Plenum Publishing Corporation, 1997 Caco-2 nationallicence absorption nationallicence prediction nationallicence human nationallicence P-glycoprotein nationallicence transport nationallicence Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 763-766 0724-8741 14:6<763 1997 14 11095 https://doi.org/10.1023/A:1012102522787 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012102522787 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Yee Shiyin Pfizer Inc., Central Research, Eastern Point Rd., 06340, Groton, Connecticut aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 763-766 0724-8741 14:6<763 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer