- Drug Metab Dispos. 2007 Feb;35(2):302-5. Epub 2006 Nov 28.
Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats.
Nagata M, Hidaka M, Sekiya H, Kawano Y, Yamasaki K, Okumura M, Arimori K.
of Pharmaceutical Sciences, Kyushu University of Health and Welfare,
1714-1 Yoshino, Nobeoka City, Miyazaki, 882-8508, Japan.
In this study, we
investigated whether pomegranate juice could inhibit CYP2C9 activity.
The ability of pomegranate juice to inhibit the diclofenac
4'-hydroxylase activity of human CYP2C9 was examined using human liver
microsomes. Pomegranate juice was shown to be a potent inhibitor of
human CYP2C9. The addition of 25 microl (5% v/v) of pomegranate juice
resulted in almost complete inhibition of human CYP2C9 activity.
addition, we investigated the effect of pomegranate juice on the
pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats.
Relative to the control group, the area under the concentration-time
curve was approximately 1.2-fold greater when pomegranate juice (3 ml)
was injected p.o. 1 h before the p.o. administration of the tolbutamide
(20 mg/kg). The elimination half-life of tolbutamide was not altered by
pomegranate juice administration. These results suggest pomegranate
juice ingestion inhibits the intestinal metabolism of tolbutamide
without inhibiting the hepatic metabolism in rats. Thus, we discovered
that pomegranate juice inhibited human CYP2C9 activity and furthermore
increased tolbutamide bioavailability in rats.