Abstract
Grapefruit juice, a beverage consumed in large quantities by the general population, is an inhibitor of the intestinal cytochrome P-450 3A4 system, which is responsible for the first-pass metabolism of many medications. Through the inhibition of this enzyme system, grapefruit juice interacts with a variety of medications, leading to elevation of their serum concentrations. Most notable are its effects on cyclosporine, some 1,4-dihydropyridine calcium antagonists, and some 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. In the case of some drugs, these increased drug concentrations have been associated with an increased frequency of dose-dependent adverse effects. The P-glycoprotein pump, located in the brush border of the intestinal wall, also transports many cytochrome P-450 3A4 substrates, and this transporter also may be affected by grapefruit juice. This review discusses the proposed mechanisms of action and the medications involved in drug-grapefruit juice interactions and addresses the clinical implications of these interactions.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects
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Beverages / adverse effects*
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Beverages / analysis
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Biological Availability
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Calcium Channel Blockers / metabolism
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Citrus / adverse effects*
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Citrus / chemistry
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Cyclosporine / metabolism
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Cytochrome P-450 CYP3A
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Cytochrome P-450 Enzyme Inhibitors
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Cytochrome P-450 Enzyme System / drug effects
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Dose-Response Relationship, Drug
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Food-Drug Interactions / physiology*
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Histamine H1 Antagonists / metabolism
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / metabolism
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Immunosuppressive Agents / metabolism
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Intestinal Mucosa / drug effects
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Intestinal Mucosa / enzymology
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Mixed Function Oxygenases / antagonists & inhibitors
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Mixed Function Oxygenases / drug effects
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Psychotropic Drugs / metabolism
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Tacrolimus / metabolism
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Terfenadine / metabolism
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Calcium Channel Blockers
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Cytochrome P-450 Enzyme Inhibitors
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Histamine H1 Antagonists
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Immunosuppressive Agents
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Psychotropic Drugs
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Terfenadine
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Cyclosporine
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Cytochrome P-450 Enzyme System
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Mixed Function Oxygenases
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CYP3A protein, human
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Cytochrome P-450 CYP3A
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Tacrolimus