Specific CYP3A4 inhibitors in grapefruit juice: Furocoumarin dimers as components of drug interaction

Katsuyuki Fukuda, Tomihisa Ohta, Yoshiteru Oshima, Noriko Ohashi, Masayoshi Yoshikawa, Yasushi Yamazoe

研究成果: Article査読

187 被引用数 (Scopus)

抄録

Four components were isolated from grapefruit juice that: inhibit human CYP3A-mediated drug oxidation. The structures of these compounds were identified as furocoumarin derivatives by absorption spectra, APCI-liquid chromatography/tandem mass spectrometry and nuclear magnetic resonance after their purification by reversed-phase high performance liquid chromatography. They include two new furocoumarins, 4-[[6-hydroxy-7-[[1-[(1-hydroxy-1-methyl) ethyl]-4-methyl-6-(7-oxo-7H-furo[3,2-g][1]benzopyran-4-yl)-4-hexenyl]oxy]-3,7 -dimethyl-2-octenyl] oxy]-7H-furo[3,2-g][1]benzopyran-7-one (GF-I-1) and 4-[[6-hydroxy-7-[[4-methyl-1-(1-methylethenyl)-6-(7-oxo-7H-furo[3,2 -g][1]benzopyran-4-yl)-4-hexenyl]oxy]-3,7-dimethyl-2-octenyl]oxy]-7H-furo[3,2 -g][1]benzopyran-7-one (GF-I-4). These furocoumarins are strong candidates for causative agents of grapefruit juice-mediated drug interaction, because of an inhibition potential that is equal to or stronger than the prototypical CYP3A4 inhibitor, ketoconazole, on liver microsomal testosterone 6β-hydroxylation.

本文言語English
ページ(範囲)391-396
ページ数6
ジャーナルPharmacogenetics
7
5
DOI
出版ステータスPublished - 1997 10 18

ASJC Scopus subject areas

  • 遺伝学
  • 薬理学、毒性学および薬学(全般)

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