title: Grapefruit-drug interactions.
abstract: Grapefruit juice and grapefruit product consumption have potential health benefits; however, their intake is also associated with interactions with certain drugs, including calcium channel blockers, immunosuppressants and antihistamines. The primary mechanism through which interactions are mediated is mechanism-based intestinal cytochrome P450 3A4 inhibition by furanocoumarins resulting in increased bioavailability of administered medications that are substrates. Grapefruit products have also been associated with interactions with P-glycoprotein (P-gp) and uptake transporters (e.g. organic anion-transporting polypeptides [OATPs]). Polyphenolic compounds such as flavonoids have been proposed as the causative agents of the P-gp and OATP interactions. The mechanisms and magnitudes of the interactions can be influenced by the concentrations of furanocoumarins and flavonoids in the grapefruit product, the volume of juice consumed, and the inherent variability of specific enzymes and transporter components in humans. It is therefore challenging to predict the extent of grapefruit product-drug interactions and to compare available in vitro and in vivo data. The clinical significance of such interactions also depends on the disposition and toxicity profile of the drug being administered. The aim of this review is to outline the mechanisms of grapefruit-drug interactions and present a comprehensive summary of those agents affected and whether they are likely to be of clinical relevance.
authors.affiliation: NIHR Biomedical Research Centre, Royal Liverpool and Broadgreen University Hospital Trust, Liverpool, UK. k.seden@liv.ac.uk
authors.forename: Kay
authors.initials: K
authors.lastname: Seden
authors.forename: Laura
authors.initials: L
authors.lastname: Dickinson
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
authors.forename: David
authors.initials: D
authors.lastname: Back
mesh_terms: D000818:Animals; D001628:Beverages; D001682:Biological Availability; D032083:Citrus paradisi / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000009:adverse effects / Q000378:metabolism; D018565:Food-Drug Interactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System