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First published on January 13, 2006; DOI: 10.1124/dmd.105.007930

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Received for publication October 21, 2005.
Revised December 19, 2005.
Accepted for publication January 12, 2006.

Inhibitory effects of fruit juices on cytochrome P450 3A (CYP3A) activity

Hyunmi Kim 1, Yune-Jung Yoon 1, Ji-Hong Shon 1, In-June Cha 1, Jae-Gook Shin 1, Kwang-Hyeon Liu 1*

1 Inje University College of Medicine

* Address correspondence to: E-mail: dstlkh{at}inje.ac.kr

Abstract

There have been very limited reports on the effects of commercial fruit juices on human cytochrome P450 3A (CYP3A) activity. Therefore, the inhibitory effects of readily available commercial fruit juices on midazolam 1`-hydroxylase activity, a marker of CYP3A, were evaluated in pooled human liver microsomes. The fruit juices investigated were black raspberry, black mulberry, plum and wild grape. White grapefruit, pomegranate and orange juice were used as positive and negative controls. The black mulberry juice showed the most potent inhibition of CYP3A except for grapefruit juice. The inhibition depended on the amount of a fruit juice added to the incubation mixture. The inhibitory potential of human CYP3A was in the order: grapefruit > black mulberry > wild grape > pomegranate > black raspberry. The IC50 values of all fruit juices tested were reduced after preincubation with microsomes in the presence of NADPH generating system, suggesting that a mechanism based inhibitory component was present in these fruit juices as in the case of grapefruit. The results suggest that like grapefruit juice, commercial fruit juices also have the potential to inhibit CYP3A-catalzyed midazolam 1`-hydroxylation. Therefore, in vivo studies investigating the interactions between fruit juices such as black mulberry and wild grape and CYP3A substrates are necessary to determine whether inhibition of CYP3A activity by fruit juices is clinically relevant.


Key words: CYP3A, cytochrome P450 catalyzed oxidations, drug interactions, enzyme inhibitors


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