title: Drug-grapefruit juice interactions.
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.
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, Minn. 55905, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Kane
authors.forename: J J
authors.initials: JJ
authors.lastname: Lipsky
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D001628:Beverages / Q000009:adverse effects* / Q000032:analysis; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000378:metabolism; D002957:Citrus / Q000009:adverse effects* / Q000737:chemistry; D016572:Cyclosporine / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018565:Food-Drug Interactions / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000187:drug effects; D011619:Psychotropic Drugs / Q000378:metabolism; D016559:Tacrolimus / Q000378:metabolism; D016593:Terfenadine / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D065607:Cytochrome P-450 Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D011619:Psychotropic Drugs; D016593:Terfenadine; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus