Potent Inhibition of Human Cytochrome P450 3A4, 2D6, and 2C9 Isoenzymes by Grapefruit Juice and Its Furocoumarins

The cytochrome P450 enzyme family is the most abundant and responsible for the metabolism of more than 60% of currently marketed drugs and is considered central in many clinically important drug interactions. Seven different grapefruit and pummelo juices as well as 5 furocoumarins isolated from grap...

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Bibliographic Details
Published in:Journal of food science 2007-10, Vol.72 (8), p.C417-C421
Main Authors: Girennavar, B., Jayaprakasha, G.K., Patil, B.S.
Format: Article
Language:English
Subjects:
Aryl Hydrocarbon Hydroxylases
Beverages
bioavailability modulators
Biological and medical sciences
Citrus fruits
Citrus paradisi - chemistry
Cytochrome P-450 CYP2D6
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme Inhibitors
cytochrome P450 inhibitors
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
Enzymes
Feeding. Feeding behavior
Food industries
Food science
Fruit and vegetable industries
Fruit juices
Fundamental and applied biological sciences. Psychology
Furocoumarins - pharmacology
grapefruit juice-drug interaction
Humans
Inhibitory Concentration 50
Organic chemicals
phase I enzymes
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:The cytochrome P450 enzyme family is the most abundant and responsible for the metabolism of more than 60% of currently marketed drugs and is considered central in many clinically important drug interactions. Seven different grapefruit and pummelo juices as well as 5 furocoumarins isolated from grapefruit juice were evaluated at different concentration on cytochrome P450 3A4 (CYP3A4), cytochrome P450 2C9 (CYP2C9), and cytochrome P450 2D6 (CYP2D6) isoenzyme activity. Grapefruit and pummelo juices were found to be potent inhibitors of cytochrome CYP3A4 and CYP2C9 isoenzymes at 25% concentration, while CYP2D6 is inhibited significantly low at all the tested concentration of juices (P < 0.05). Among the 5 furocoumarins tested, the inhibitory potency was in the order of paradisin A > dihydroxybergamottin > bergamottin > bergaptol > geranylcoumarin at 0.1 μM to 0.1 mM concentrations. The IC50 value was lowest for paradisin A for CYP3A4 with 0.11 μM followed by DHB for CYP2C9 with 1.58 μM.
ISSN:0022-1147
1750-3841
DOI:10.1111/j.1750-3841.2007.00483.x