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Drug Metabolism and Disposition Fast Forward
First published on December 2, 2005; DOI: 10.1124/dmd.105.006486

0090-9556/06/3403-343-345$20.00
DMD 34:343-345, 2006

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SHORT COMMUNICATION

TRANSIENT INHIBITION OF CYP3A IN RATS BY STAR FRUIT JUICE

Muneaki Hidaka, Manabu Okumura, Tetsuya Ogikubo, Hirofumi Kai, Ken-Ichi Fujita, Tomomi Iwakiri, Keishi Yamasaki, Nao Setoguchi, Naoya Matsunaga, and Kazuhiko Arimori

Department of Pharmacy, Miyazaki Medical College Hospital, Miyazaki, Japan (M.H., M.O., T.O., K.F., T.I., K.Y., N.S., N.M., K.A.); and Department of Molecular Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan (H.K.)

Star fruit juice is a potent in vitro inhibitor of CYP3A; however, few reports are available on the inhibition of CYP3A activities by star fruit juice in vivo. Therefore, in this study, we investigated the CYP3A-mediated star fruit-drug interaction in vivo. The effect of star fruit juice on carbamazepine pharmacokinetics was examined in rats. In comparison with water, the area under the concentration-time curve (AUC) of carbamazepine was approximately 1.3-fold greater when star fruit juice (2 ml) was orally administered 1 h before the oral administration of carbamazepine (50 mg/kg). In contrast, the elimination half-life of carbamazepine and the AUC ratio of carbamazepine 10,11-epoxide to carbamazepine were not altered by the administration of star fruit juice. These results suggest that star fruit juice impairs the function of enteric CYP3A, but not of hepatic CYP3A. In addition, we evaluated the time course of recovery of CYP3A activity that was reduced after the treatment with star fruit juice. The inhibition by star fruit juice was recovered within approximately 24 h. These data suggest that the effect of star fruit juice is mainly reversible and transient. Thus, we discovered that star fruit juice alters the carbamazepine pharmacokinetics in rats.

Address correspondence to: Muneaki Hidaka, Department of Pharmacy, Miyazaki Medical College Hospital, 5200 Kihara, Kiyotake-cho, Miyazaki-gun, 889-1692, Japan. E-mail: yshidaka{at}med.miyazaki-u.ac.jp




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M. Nagata, M. Hidaka, H. Sekiya, Y. Kawano, K. Yamasaki, M. Okumura, and K. Arimori
Effects of Pomegranate Juice on Human Cytochrome P450 2C9 and Tolbutamide Pharmacokinetics in Rats
Drug Metab. Dispos., February 1, 2007; 35(2): 302 - 305.
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