Involvement of the CYP1A Subfamily in Stereoselective Metabolism of Carvedilol in .BETA.-Naphthoflavone-Treated Caco-2 Cells

• Ishida Kazuya

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

• Taguchi Masato

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

• Akao Teruaki

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

• Hashimoto Yukiya

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

Bibliographic Information

Other Title

• Involvement of the CYP1A subfamily in stereoselective metabolism of carvedilol in β-naphthoflavone-treated Caco-2 cells
• Involvement of the CYP1A subfamily in stereoselective metabolism of carvedilol in v naphthoflavone treated Caco 2 cells

Abstract

We have previously reported that the metabolism of S-carvedilol in β-naphthoflavone (β-NF)-treated Caco-2 cells is faster than that of R-carvedilol. The aim of the present study was to identify the enzyme responsible for the stereoselective metabolism of carvedilol in the cells. The expression of cytochrome P450 (CYP) 1A1 and CYP1A2 mRNA, but not CYP2D6, CYP3A4, and CYP2C9 mRNA, was increased in β-NF-treated Caco-2 cells, as compared with non-treated cells. Furafylline, an inhibitor of the CYP1A subfamily, decreased the metabolism of S-carvedilol in Caco-2 cells cultured on plastic dishes. In addition, the glucuronidation of carvedilol was not significant in microsomes of β-NF-treated Caco-2 cells. On the other hand, the oxidation of S-carvedilol in microsomes of β-NF-treated Caco-2 cells was faster than that of R-carvedilol, and furafylline decreased the oxidative activity of S-carvedilol. These findings suggested that the CYP1A subfamily was responsible for the stereoselective metabolism of carvedilol in β-NF-treated Caco-2 cells.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 32 (3), 513-516, 2009

  The Pharmaceutical Society of Japan

Keywords

• carvedilol
• Caco-2 cell
• stereoselective metabolism
• cytochrome P450

Details

• CRID: 1390001204625005568
• NII Article ID: 110007122683
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.32.513
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 10166647
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10166647
• Web Site: http://www.jstage.jst.go.jp/article/bpb/32/3/32_3_513/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2009216345
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed