Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells

J Pharm Sci. 2007 Oct;96(10):2808-17. doi: 10.1002/jps.20975.


To investigate the potential interaction between selected ingredients of grapefruit juice and, the transport of talinolol, a P-gp substrate, across Caco-2 cells monolayers was determined in the absence and presence of distinct concentrations of grapefruit juice, bergamottin, 6',7'-dihydroxybergamottin, 6',7'-epoxybergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6',7'-epoxybergamottin, was the most potent inhibitor (IC(50) = 0.7 microM), followed by 6',7'-dihydroxybergamottin (IC(50) = 34 microM) and bergamottin that did not show any inhibition at concentrations up to 10 microM. The flavonoid aglycone naringenin was around 10-fold more potent than its glycoside naringin with IC(50) values of 236 and 2409 microM, respectively. The flavonoids and furanocoumarins tested in this study are in the same range of concentration they are present in the juice contributing, therefore, for the overall inhibitory effect of GFJ on P-gp activity. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P-gp activity modifying the disposition of drugs that are P-gp substrates such as talinolol.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Beverages*
  • Caco-2 Cells
  • Citrus paradisi*
  • Dose-Response Relationship, Drug
  • Flavanones / pharmacology
  • Food-Drug Interactions*
  • Furocoumarins / pharmacology
  • Humans
  • Intestinal Absorption / drug effects*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Membrane Transport Modulators / pharmacology*
  • Permeability
  • Propanolamines / metabolism*


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Flavanones
  • Furocoumarins
  • Membrane Transport Modulators
  • Propanolamines
  • epoxybergamottin
  • talinolol
  • naringenin
  • bergamottin
  • naringin
  • 6',7'-dihydroxybergamottin