Grapefruit juice–drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells
✍ Scribed by Whocely Victor de Castro; Susanne Mertens-Talcott; Hartmut Derendorf; Veronika Butterweck
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 163 KB
- Volume
- 96
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
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 0 ,7 0 -dihydroxybergamottin, 6 0 ,7 0 -epoxybergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6 0 ,7 0 -epoxybergamottin, was the most potent inhibitor (IC 50 ¼ 0.7 mM), followed by 6 0 ,7 0 -dihydroxybergamottin (IC 50 ¼ 34 mM) and bergamottin that did not show any inhibition at concentrations up to 10 mM. The flavonoid aglycone naringenin was around 10-fold more potent than its glycoside naringin with IC 50 values of 236 and 2409 mM, 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.