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Major active components in grapefruit, orange, and apple juices responsible for OATP2B1-mediated drug interactions.

Abstract

We aimed to explore the major active components in grapefruit juice (GFJ), orange juice (OJ), and apple juice (AJ) that are responsible for OATP2B1-mediated drug interactions, by means of in vitro studies using Xenopus oocytes expressing OATP2B1 with a typical OATP2B1 substrate, estrone-3-sulfate. All three juices inhibited OATP2B1-mediated estrone-3-sulfate uptake with half-maximum inhibition (IC(50) ) 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 OATP2B1-mediated estrone-3-sulfate uptake with IC(50) values of 4.63, 49.2, 1.92, 67.6, 23.2, 1.31, 9.47, and 21.3 µM, respectively. When the concentration-IC(50) ratios ([C]/IC(50) ) of these flavonoids in GFJ, OJ, and AJ were calculated, values of [C]/IC(50) ≥ 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.

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  • Publisher Full Text
  • Authors

    Shirasaka Y, Shichiri M, Mori T, Nakanishi T, Tamai I

    Source

    Journal of pharmaceutical sciences 102:1 2013 Jan pg 280-8

    MeSH

    Animals
    Beverages
    Citrus paradisi
    Citrus sinensis
    Dose-Response Relationship, Drug
    Estrone
    Flavanones
    Flavonoids
    Food-Drug Interactions
    Fruit
    Hesperidin
    Humans
    Kinetics
    Least-Squares Analysis
    Malus
    Models, Biological
    Nonlinear Dynamics
    Oocytes
    Organic Anion Transporters
    Osmolar Concentration
    Phlorhizin
    Quercetin
    Xenopus laevis

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    23132664