Fukuda K, Ohta T, Oshima Y, Ohashi N, Yoshikawa M, Yamazoe Y
Division of Drug Metabolism and Molecular Toxicology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Pharmacogenetics. 1997 Oct;7(5):391-6. doi: 10.1097/00008571-199710000-00008.
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-dimeth yl- 2-octenyl] oxy]-7H-furo[3,2-g][1]benzopyran-7-one (GF-I-1) and 4-[[6-hydroxy-7-[[4-methyl-I- (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 6 beta-hydroxylation.
从葡萄柚汁中分离出了四种抑制人CYP3A介导的药物氧化的成分。通过反相高效液相色谱法纯化后，利用吸收光谱、大气压化学电离液相色谱/串联质谱法和核磁共振法确定了这些化合物的结构为呋喃香豆素衍生物。它们包括两种新的呋喃香豆素，4-[[6-羟基-7-[[1-[(1-羟基-1-甲基)乙基]-4-甲基-6-(7-氧代-7H-呋喃并[3,2-g][1]苯并吡喃-4-基)-4-己烯基]氧基]-3,7-二甲基-2-辛烯基]氧基]-7H-呋喃并[3,2-g][1]苯并吡喃-7-酮（GF-I-1）和4-[[6-羟基-7-[[4-甲基-1-(1-甲基乙烯基)-6-(7-氧代-7H-呋喃并[3,2-g][1]苯并吡喃-4-基)-4-己烯基]氧基]-3,7-二甲基-2-辛烯基]氧基]-7H-呋喃并[3,2-g][1]苯并吡喃-7-酮（GF-I-4）。这些呋喃香豆素很可能是葡萄柚汁介导的药物相互作用的致病因子，因为它们对肝微粒体睾酮6β-羟基化的抑制潜力与典型的CYP3A4抑制剂酮康唑相当或更强。
