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

Kazuya Ishida, Masato Taguchi, Teruaki Akao, Yukiya Hashimoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Pages (from-to)513-516
Number of pages4
JournalBiological and Pharmaceutical Bulletin
Volume32
Issue number3
DOIs
StatePublished - 2009/03

Keywords

  • Caco-2 cell
  • Carvedilol
  • Cytochrome P450
  • Stereoselective metabolism

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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