Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485459 | Journal of Pharmaceutical Sciences | 2013 | 9 Pages |
Abstract
We aimed to explore the major active components in grapefruit juice (GFJ), orange juice (OJ), and apple juice (AJ) that are responsible for OATP2B1âmediated drug interactions, by means of in vitro studies using Xenopus oocytes expressing OATP2B1 with a typical OATP2B1 substrate, estroneâ3âsulfate. All three juices inhibited OATP2B1âmediated estroneâ3âsulfate uptake with halfâmaximum inhibition (IC50) values of 0.222% (GFJ), 0.807% (OJ), and 2.27% (AJ). Eight major flavonoids (naringin, naringenin, hesperidin, hesperetin, phloridzin, phloretin, quercetin, and kaempferol) contained in the juices inhibited OATP2B1âmediated estroneâ3âsulfate uptake with IC50 values of 4.63, 49.2, 1.92, 67.6, 23.2, 1.31, 9.47, and 21.3 µM, respectively. When the concentration-IC50 ratios ([C]/IC50) of these flavonoids in GFJ, OJ, and AJ were calculated, values of [C]/IC50 ⥠100 were obtained for naringin in GFJ and hesperidin in OJ. No flavonoid in AJ showed a ratio higher than unity. However, significant inhibition of OATP2B1 was observed with a mixture of phloridzin, phloretin, hesperidin, and quercetin at the concentrations present in AJ. In conclusion, our results indicate that naringin and hesperidin are the major OATP2B1 inhibitors in GFJ and OJ, respectively, whereas a combination of multiple components appears to be responsible for OATP2B1 inhibition by AJ.
Keywords
Related Topics
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Yoshiyuki Shirasaka, Megumi Shichiri, Takanori Mori, Takeo Nakanishi, Ikumi Tamai,