Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects.
OBJECTIVE
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.
Ushijima
Kentarou
K
Molecular Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan.
Tsuruoka
Shu-ichi
S
Tsuda
Hidetoshi
H
Hasegawa
Gohki
G
Obi
Yuri
Y
Kaneda
Tae
T
Takahashi
Masaki
M
Maekawa
Tomohiro
T
Sasaki
Tomohiro
T
Koshimizu
Taka-aki
TA
Fujimura
Akio
A
D000284:Administration, Oral; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001628:Beverages; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D065729:Cytochrome P-450 CYP2C9; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D004812:Epidemiologic Methods; D005260:Female; D018565:Food-Drug Interactions / Q000502:physiology; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010936:Plant Extracts / Q000378:metabolism*; D029799:Vaccinium macrocarpon / Q000378:metabolism*; D055815:Young Adult
D016861:Cyclooxygenase Inhibitors; D010936:Plant Extracts; D004008:Diclofenac; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases
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