caa a22 4500 477127703 CHVBK 20180405111654.0 cr unu---uuuuu 170330e19970801xx s 000 0 eng 10.1023/A:1012197110917 doi (NATIONALLICENCE)springer-10.1023/A:1012197110917 Comparison of CYP3A Activities in a Subclone of Caco-2 Cells (TC7) and Human Intestine [Elektronische Daten] [Shamsi Raeissi, Zuyu Guo, Glenn Dobson, Per Artursson, Ismael Hidalgo] Purpose. To compare the activity of the CYP3A enzyme expressed by TC7, a cell culture model of the intestinal epithelial cell, to the activity of human intestinal CYP3A4, using terfenadine as a substrate. Methods. The metabolism of terfenadine was investigated in intact cells and microsomal preparations from TC7, human intestine, and liver. The effect of two CYP3A inhibitors, ketoconazole and troleandomycin (TAO), on the metabolism of terfenadine was also examined. Results. Only hydroxy-terfenadine was detected in TC7 microsomal incubations. In contrast, azacyclonol and hydroxy-terfenadine were detected in human intestinal and hepatic microsomal incubations. The Km values for hydroxy-terfenadine formation in TC7 cells, intestine and liver microsomes were 1.91, 2.5, and 1.8, μM respectively. The corresponding Vmax values were 2.11, 61.0, and 370 pmol/min/mg protein. Km values for azacyclonol in intestinal and hepatic samples were 1.44 and 0.82 μM and the corresponding Vmax values were 14 and 60 pmol/min/mg protein. The formation of hydroxy-terfenadine was inhibited by ketoconazole and TAO in human intestine and TC7 cell microsomes. The Km and Vmax values for terfenadine metabolism in intact TC7 cells were similar to those from TC7 cell microsomes. Conclusions. Our results indicate that TC7 cells are a potentially useful alternative model for studies of CYP3A mediated drug metabolism. The CYP3A expressed by TC7 cells is not CYP3A4, but probably CYP3A5, making this cell line suitable for studies of colonic drug transport and metabolism. Plenum Publishing Corporation, 1997 TC7 nationallicence Caco-2 nationallicence CYP3A nationallicence terfenadine nationallicence intestinal metabolism nationallicence Raeissi Shamsi Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Central Research, 19426-0107, Collegeville, Pennsylvania aut Guo Zuyu Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Central Research, 19426-0107, Collegeville, Pennsylvania aut Dobson Glenn Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Central Research, 19426-0107, Collegeville, Pennsylvania aut Artursson Per Department of Pharmaceutics, Uppsala University, Sweden aut Hidalgo Ismael Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Central Research, 19426-0107, Collegeville, Pennsylvania aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/8(1997-08-01), 1019-1025 0724-8741 14:8<1019 1997 14 11095 https://doi.org/10.1023/A:1012197110917 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012197110917 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Raeissi Shamsi Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Central Research, 19426-0107, Collegeville, Pennsylvania aut NATIONALLICENCE 700 1- Guo Zuyu Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Central Research, 19426-0107, Collegeville, Pennsylvania aut NATIONALLICENCE 700 1- Dobson Glenn Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Central Research, 19426-0107, Collegeville, Pennsylvania aut NATIONALLICENCE 700 1- Artursson Per Department of Pharmaceutics, Uppsala University, Sweden aut NATIONALLICENCE 700 1- Hidalgo Ismael Drug Metabolism and Pharmacokinetics, Rhone-Poulenc Rorer Central Research, 19426-0107, Collegeville, Pennsylvania aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/8(1997-08-01), 1019-1025 0724-8741 14:8<1019 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer