RRC ID 43131
著者 Ishida K, Honda M, Shimizu T, Taguchi M, Hashimoto Y.
タイトル Stereoselective metabolism of carvedilol by the beta-naphthoflavone-inducible enzyme in human intestinal epithelial Caco-2 cells.
ジャーナル Biol Pharm Bull
Abstract Treatment of Caco-2 cells with beta-naphthoflavone (beta-NF) and 1alpha,25-dihydroxyvitamin D(3) (VD(3)) induces UDP-glucuronosyltransferases (UGTs) and cytochrome P450 (CYP) 3A4, respectively. In the present study, we evaluated the metabolism of carvedilol in beta-NF- and VD(3)-treated Caco-2 cells. The metabolism of R-carvedilol was not significant in non-treated Caco-2 cells, whereas S-carvedilol was significantly metabolized in the cells. The metabolism of R- and S-carvedilol was significantly increased by the treatment of Caco-2 cells with 50 microM beta-NF for 3 d. In contrast, the treatment of Caco-2 cells with 250 nM VD(3) for 2 weeks did not induce a significant change in the metabolism of R- and S-carvedilol. The metabolism of carvedilol in beta-NF-treated Caco-2 cells was markedly inhibited by a substrate of UGTs, baicalein. In addition, the expression of UGT1A1, 1A6, and 1A9 mRNA was increased in beta-NF-treated Caco-2 cells as compared with non-treated cells. These findings indicated that carvedilol was metabolized stereoselectively by the beta-NF-inducible enzyme in Caco-2 cells. The UGT1A subfamily in intestinal epithelial cells may be partly responsible for first-pass (presystemic) metabolism of the drug.
巻・号 30(10)
ページ 1930-3
公開日 2007-10-1
DOI 10.1248/bpb.30.1930
PII JST.JSTAGE/bpb/30.1930
PMID 17917264
MeSH Adrenergic beta-Antagonists / pharmacokinetics* Biotransformation Caco-2 Cells Calcitriol / pharmacology Carbazoles / pharmacokinetics* Carvedilol Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System / biosynthesis Enzyme Induction / drug effects Enzyme Inhibitors / pharmacology Flavanones / pharmacology Glucuronosyltransferase / antagonists & inhibitors Glucuronosyltransferase / biosynthesis Humans Isoenzymes / biosynthesis Propanolamines / pharmacokinetics* RNA, Messenger / biosynthesis Reverse Transcriptase Polymerase Chain Reaction Stereoisomerism beta-Naphthoflavone / pharmacology*
IF 1.863
引用数 5
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 CACO-2(RCB0988)