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Takayama K, Ito K, Matsui A, et al. In Vivo Gene Expression Profile of Human Intestinal Epithelial Cells: From the Viewpoint of Drug Metabolism and Pharmacokinetics. Drug Metab Dispos. 2020;49(3):221-232doi: 10.1124/dmd.120.000283.
Takayama, K., Ito, K., Matsui, A., Yamashita, T., Kawakami, K., Hirayama, D., Kishimoto, W., Nakase, H., & Mizuguchi, H. (2021). In Vivo Gene Expression Profile of Human Intestinal Epithelial Cells: From the Viewpoint of Drug Metabolism and Pharmacokinetics. Drug metabolism and disposition: the biological fate of chemicals, 49(3), 221-232. https://doi.org/10.1124/dmd.120.000283
Takayama, Kazuo, et al. "In Vivo Gene Expression Profile of Human Intestinal Epithelial Cells: From the Viewpoint of Drug Metabolism and Pharmacokinetics." Drug metabolism and disposition: the biological fate of chemicals vol. 49,3 (2021): 221-232. doi: https://doi.org/10.1124/dmd.120.000283
Takayama K, Ito K, Matsui A, Yamashita T, Kawakami K, Hirayama D, Kishimoto W, Nakase H, Mizuguchi H. In Vivo Gene Expression Profile of Human Intestinal Epithelial Cells: From the Viewpoint of Drug Metabolism and Pharmacokinetics. Drug Metab Dispos. 2021 Mar;49(3):221-232. doi: 10.1124/dmd.120.000283. Epub 2020 Dec 31. PMID: 33384384.
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Drug Metab Dispos. 2021 Mar;49(3):221-232. doi: 10.1124/dmd.120.000283. Epub 2020 Dec 31.

In Vivo Gene Expression Profile of Human Intestinal Epithelial Cells: From the Viewpoint of Drug Metabolism and Pharmacokinetics.

Drug metabolism and disposition: the biological fate of chemicals

Kazuo Takayama, Kohei Ito, Akiko Matsui, Tomoki Yamashita, Kentaro Kawakami, Daisuke Hirayama, Wataru Kishimoto, Hiroshi Nakase, Hiroyuki Mizuguchi

Affiliations

  1. Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan (K.T., T.Y., H.M.); Laboratory of Hepatocyte Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan (K.T., H.M.); Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co., Ltd., Kobe, Japan (K.I., A.M., W.K.); Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan (K.K., D.H., H.N.); and Global Center for Medical Engineering and Informatics (H.M.) and Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI) (H.M.), Osaka University, Osaka, Japan.
  2. Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan (K.T., T.Y., H.M.); Laboratory of Hepatocyte Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan (K.T., H.M.); Department of Pharmacokinetics and Nonclinical Safety, Nippon Boehringer Ingelheim Co., Ltd., Kobe, Japan (K.I., A.M., W.K.); Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan (K.K., D.H., H.N.); and Global Center for Medical Engineering and Informatics (H.M.) and Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI) (H.M.), Osaka University, Osaka, Japan [email protected] [email protected] [email protected].

PMID: 33384384 DOI: 10.1124/dmd.120.000283

Abstract

Orally administered drugs are absorbed and metabolized in the intestine. To accurately predict pharmacokinetics in the intestine, it is essential to understand the intestinal expression profiles of the genes related to drug absorption, distribution, metabolism, and excretion (ADME). However, in many previous studies, gene expression analysis in the intestine has been carried out using specimens from patients with cancer. In this study, to obtain more accurate gene expression profiles, biopsy samples were collected under endoscopic observation from the noninflammatory regions of 14 patients with inflammatory bowel disease, and RNA-seq analysis was performed. Gene expression analysis of drug-metabolizing enzymes (cytochromes P450), non-cytochrome P450 enzymes, nuclear receptors, drug-conjugating enzymes (UDP-glucuronosyltransferases and sulfotransferases), and apical and basolateral drug transporters was performed in biopsy samples from the duodenum, ileum, colon, and rectum. The proportions of the cytochromes P450 expressed in the ileum were 25% (

Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.

Conflict of interest statement

No author has an actual or perceived conflict of interest with the contents of this article.

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