Grapefruit Juice-Drug Interactions: Grapefruit Juice and Its Components Inhibit P‐Glycoprotein (ABCB1) Mediated Transport of Talinolol in Caco‐2 Cells

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 (IC50 = 0.7 µM), followed by 6′,7′‐dihydroxybergamottin (IC50 = 34 µM) and bergamottin that did not show any inhibition at concentrations up to 10 µM. The flavonoid aglycone naringenin was around 10‐fold more potent than its glycoside naringin with IC50 values of 236 and 2409 µM, 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. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2808-2817, 2007