Amounts and variation in grapefruit juice of the main components causing grapefruit-drug interaction.
A method for the determination of three furocoumarins containing two new chemicals (GF-I-1 and GF-I-4) in commercially available grapefruit juice and grapefruit itself was developed using high-performance liquid chromatography (HPLC). These components isolated from grapefruit juice have 5-geranyloxyfurocoumarin dimer structures showing extremely high affinities for a form of cytochrome P450 (CYP3A4). Considerable differences were observed on the contents among commercial brands and also batches. The contents were determined to be 321.4+/-95.2 ng/ml GF-I-1, 5641.2+/-1538.1 ng/ml GF-I-2 and 296.3+/-84.9 ng/ml GF-I-4 in twenty-eight white grapefruit juices. These chemicals were not detected in beverages from orange, apple, grape and tangerine, except that trace amount of GF-I-2 and GF-I-4 were found in lemon juice. The average levels of these furocoumarins were lower in the juice from red grapefruit than a white one. The highest level of these components were found in the fruit meat.
Fukuda
K
K
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. k-fukuda@tanabe.co.jp
Guo
L
L
Ohashi
N
N
Yoshikawa
M
M
Yamazoe
Y
Y
D001628:Beverages / Q000032:analysis*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D002957:Citrus; D003374:Coumarins / Q000032:analysis* / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018565:Food-Drug Interactions; D013058:Mass Spectrometry; D006899:Mixed Function Oxygenases / Q000378:metabolism; D015203:Reproducibility of Results; D013379:Substrate Specificity
D003374:Coumarins; C413758:GF I-1; C413759:GF I-4; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human