title: Food-drug interactions: grapefruit juice.
abstract: Food-drug interactions are increasingly recognized as important clinical events which may change significantly the bioavailability of oral administrated drugs. Grapefruit juice (GFJ) demonstrated multiple interactions with drugs leading to loss of the therapeutic effects or increased side-effects. GFJ decreases pre-systemic metabolism through a) competitive or mechanism-based inhibition of gut wall CYP3A4 isoenzymes and b) P-glycoprotein (P-gp), c) multidrug resistance protein-2 (MRP2) or d) organic anion-transporting polypeptide (OATP) inhibition. Although, GFJ presents high amounts of flavonoids (e.g. naringin, naringenin), furanocoumarins (e.g. 6',7'-dihydroxybergamottin, bergamottin) are the main chemicals involved in the pharmacokinetic interactions. As compounds of GFJ show additive or synergistic effects, all the major furanocoumarins are necessary for the maximal inhibitory effect. Also, related citrus fruits (sweeties, pummelo and sour orange) or various plants containing furanocoumarins may present pharmacological interactions, yet to be discovered.
authors.affiliation: School of Pharmacy, Department of Environmental and Food Chemistry, Gr.T.Popa University of Medicine and Pharmacy Iasi.
authors.forename: Camelia Harapu
authors.initials: CH
authors.lastname: Diaconu
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cuciureanu
authors.forename: L
authors.initials: L
authors.lastname: Vlase
authors.forename: Rodica
authors.initials: R
authors.lastname: Cuciureanu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism; D001628:Beverages; D032083:Citrus paradisi; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000009:adverse effects; D018565:Food-Drug Interactions; D011564:Furocoumarins / Q000009:adverse effects; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism*; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051544:Cytochrome P-450 CYP3A; D005419:Flavonoids; D011564:Furocoumarins; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C510163:CYP3A4 protein, human; C068337:bergamottin; C104774:6',7'-dihydroxybergamottin