caa a22 4500 477127525 CHVBK 20180405111654.0 cr unu---uuuuu 170330e19970401xx s 000 0 eng 10.1023/A:1012103700981 doi (NATIONALLICENCE)springer-10.1023/A:1012103700981 Analysis of Drug Permeation Across Caco-2 Monolayer: Implication for Predicting In Vivo Drug Absorption [Elektronische Daten] [Shinji Yamashita, Yoshihiro Tanaka, Yoriko Endoh, Yoko Taki, Toshiyasu Sakane, Tanekazu Nadai, Hitoshi Sezaki] Purpose. The aim of the present work is to characterize in vitro drug permeation processes across Caco-2 monolayer and to identify the advantages of this cultured cell system in predicting in vivo drug absorption after oral administration. Methods. The passive permeability of various drugs through Caco-2 monolayer was measured using Ussing-type chambers and compared with that of the isolated rat jejunum and colon. The in vivo drug permeability to the intestinal membrane was estimated by means of an intestinal perfusion study using the rat jejunum. Results. In Caco-2 monolayer, drug permeability increased with increasing drug lipophilicity and showed a good linear relationship with the in vivo permeability. In contrast, in the isolated jejunum and colon, the permeability of high lipophilic drugs was almost constant and, propranolol, a drug with the highest lipophilicity, hardly passed through the jejunal membrane in vitro. As a result, there was no significant relationship between in vitro and in vivo drug permeability in rat jejunum. However, the amount of drugs accumulated in the jejunal mucosa increased with increasing drug lipophilicity even under the in vitro condition. Conclusions. The permeation and the accumulation studies suggested that the rate-limiting process of in vitro permeation of lipophilic drugs through the intestinal membrane differs from that of in vivo drug absorption. On the other hand, drug permeation through Caco-2 monolayer, which consists of an epithelial cell layer and a supporting filter, is essentially the same process as that of in vivo drug absorption. We concluded that the simple monolayer structure of a cultured cell system provides a distinct advantage in predicting in vivo drug absorption. Plenum Publishing Corporation, 1997 Caco-2 monolayer nationallicence intestinal membrane nationallicence drug lipophilicity nationallicence in vitro drug permeability nationallicence in vivo drug absorption nationallicence Yamashita Shinji Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut Tanaka Yoshihiro Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut Endoh Yoriko Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut Taki Yoko Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut Sakane Toshiyasu Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut Nadai Tanekazu Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut Sezaki Hitoshi Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 486-491 0724-8741 14:4<486 1997 14 11095 https://doi.org/10.1023/A:1012103700981 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012103700981 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamashita Shinji Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut NATIONALLICENCE 700 1- Tanaka Yoshihiro Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut NATIONALLICENCE 700 1- Endoh Yoriko Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut NATIONALLICENCE 700 1- Taki Yoko Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut NATIONALLICENCE 700 1- Sakane Toshiyasu Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut NATIONALLICENCE 700 1- Nadai Tanekazu Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut NATIONALLICENCE 700 1- Sezaki Hitoshi Faculty of Pharmaceutical Sciences, Setsunan University, 573-01, Nagaotoge-cho, Hirakata, Osaka, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 486-491 0724-8741 14:4<486 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer