Inhibitory Effects of Fruit Juices on Cytochrome P450 2C9 Activity<i>in Vitro</i>

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  • HIDAKA Muneaki
    School of Pharmaceutical Sciences, Kyushu University of Health and Welfare Department of Molecular Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University Department of Pharmacy, University of Miyazaki Hospital
  • NAGATA Masashi
    School of Pharmaceutical Sciences, Kyushu University of Health and Welfare Department of Pharmacy, University of Miyazaki Hospital
  • KAWANO Yohei
    Department of Pharmacy, University of Miyazaki Hospital
  • SEKIYA Hiroshi
    Department of Pharmacy, University of Miyazaki Hospital
  • KAI Hirofumi
    Department of Molecular Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University
  • YAMASAKI Keishi
    Department of Pharmacy, University of Miyazaki Hospital
  • OKUMURA Manabu
    Department of Pharmacy, University of Miyazaki Hospital
  • ARIMORI Kazuhiko
    Department of Pharmacy, University of Miyazaki Hospital

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  • Inhibitory Effects of Fruit Juices on Cytochrome P450 2C9 Activity in Vitro

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There is limited information on the effect of fruits on human cytochrome P450 (CYP) 2C9 activity. The objective of this study was to determine the effect of fruit juice on CYP2C9-mediated drug metabolism. Nine citrus fruits and eight tropical fruits were chosen. We investigated effects of the fruits on diclofenac 4′-hydroxylation and tolbutamide hydroxylation by human liver microsomes. Among the fruits, pineapple juice showed potent inhibition of CYP2C9 activity. The addition of 25 μl (5.0% v/v) of pineapple juice resulted in almost complete inhibition. Next we examined the inhibitory effect of bromelain, a cysteine protease in pineapple. Bromelain also strongly inhibited CYP2C9 activity. In addition, E-64, a cysteine protease inhibitor, almost entirely blocked inhibition by pineapple juice and bromelain. Thus we found that pineapple juice was a potent inhibitor of CYP2C9, and that the inhibitory effect might be due to the bromelain contained in pineapple.

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