TY - JOUR T1 - Effects of Pomegranate Juice on Human Cytochrome P450 2C9 and Tolbutamide Pharmacokinetics in Rats JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 302 LP - 305 DO - 10.1124/dmd.106.011718 VL - 35 IS - 2 AU - Masashi Nagata AU - Muneaki Hidaka AU - Hiroshi Sekiya AU - Yohei Kawano AU - Keishi Yamasaki AU - Manabu Okumura AU - Kazuhiko Arimori Y1 - 2007/02/01 UR - http://dmd.aspetjournals.org/content/35/2/302.abstract N2 - 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 μl (5% v/v) of pomegranate juice resulted in almost complete inhibition of human CYP2C9 activity. In 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. The American Society for Pharmacology and Experimental Therapeutics ER -