Content of CYP3A4 inhibitors, naringin, naringenin and bergapten in grapefruit and grapefruit juice products.
The flavonoids, naringin and naringenin and the furanocoumarin, bergapten (5-methoxypsoralen), were detected in some fresh grapefruit and commercial grapefruit juices but were not detected in other fruit juices tested (orange; orange with apple base; dark grape; orange and mango with apple base; orange, peach, passion fruit juice). The contents of these three grapefruit constituents in commercial juice and fresh grapefruit varied from brand to brand and also from lot to lot. Juice was prepared from the fresh fruit via different methods (by hand, squeezer or blender). The naringin content, after hand-squeeze, ranged from 115 to 384 mg/l. With hand-squeeze juice production, bergapten was not detected (less than 0.5 mg/l) in two varieties of grapefruit, and naringenin was usually not in detectable levels (less than 2 mg/l) in three varieties. All three constituents were present in New Zealand grapefruit preparations (including juice by hand-squeeze) and different lots showed variation in content (1.5-, 2.3- and 4.7-fold for naringin, naringenin and bergapten, respectively). Differences in the concentrations of these three constituents, which have potential for drug interaction, may contribute to the variability in pharmacokinetics of CYP3A4 drugs and some contradictory results of drug interaction studies with grapefruit juice.
Ho
P C
PC
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Saville
D J
DJ
Coville
P F
PF
Wanwimolruk
S
S
D000078223:5-Methoxypsoralen; D000975:Antioxidants / Q000032:analysis*; D001628:Beverages / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D002957:Citrus / Q000737:chemistry*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000032:analysis*; D004965:Estrogen Antagonists / Q000032:analysis*; D044950:Flavanones; D005419:Flavonoids / Q000032:analysis*; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000032:analysis; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D012015:Reference Standards
D000975:Antioxidants; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D044950:Flavanones; D005419:Flavonoids; D000078223:5-Methoxypsoralen; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C005273:naringenin; C005274:naringin; D008730:Methoxsalen