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Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects
Author(s) -
Ushijima Kentarou,
Tsuruoka Shuichi,
Tsuda Hidetoshi,
Hasegawa Gohki,
Obi Yuri,
Kaneda Tae,
Takahashi Masaki,
Maekawa Tomohiro,
Sasaki Tomohiro,
Koshimizu Takaaki,
Fujimura Akio
Publication year - 2009
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2009.03436.x
Subject(s) - cranberry juice , diclofenac , pharmacokinetics , microsome , pharmacology , chemistry , metabolism , cyp2c9 , drug metabolism , biochemistry , in vitro , cytochrome p450 , medicine , urinary system
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Cranberry juice has a significant inhibitory effect on CYP2C9 activity in vitro , whereas it shows a minimal effect on the pharmacokinetics and pharmacodynamics of warfarin, a CYP2C9 substrate in vivo . • Information regarding the interaction between cranberry juice and other medications metabolized by CYP2C9 is limited. WHAT THIS STUDY ADDS • Cranberry juice suppressed the metabolism of diclofenac, another CYP2C9 substrate, by human liver microsomes. • Pharmacokinetic parameters of diclofenac were not altered by cranberry juice consumption in human subjects. AIM To investigate a potential interaction between cranberry juice and diclofenac, a substrate of CYP2C9. METHODS The inhibitory effect of cranberry juice on diclofenac metabolism was determined using human liver microsome assay. Subsequently, we performed a clinical trial in healthy human subjects to determine whether the repeated consumption of cranberry juice changed the diclofenac pharmacokinetics. RESULTS Cranberry juice significantly suppressed diclofenac metabolism by human liver microsomes. On the other hand, repeated consumption of cranberry juice did not influence the diclofenac pharmacokinetics in human subjects. CONCLUSIONS Cranberry juice inhibited diclofenac metabolism by human liver microsomes, but not in human subjects. Based on the present and previous findings, we think that although cranberry juice inhibits CYP2C9 activity in vitro , it does not change the pharmacokinetics of medications metabolized by CYP2C9 in clinical situations.