Fruit juices and drug metabolism

[Guest guest]

I found this pretty interesting.

It appears grapefruit juice isn't the only inhibitor.

Barb

Drug Metabolism and Disposition Fast Forward

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

INHIBITORY EFFECTS OF FRUIT JUICES ON CYP3A ACTIVITY

Hyunmi Kim, Yune-Jung Yoon, Ji-Hong Shon, In-June Cha, Jae-Gook Shin,

and Kwang-Hyeon Liu

Department of Pharmacology and PharmacoGenomics Research Center, Inje

University College of Medicine, Busan, Korea

There have been very limited reports on the effects of commercial

fruit juices on human 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 the 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.