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Food and Drug Interactions: Effect of Acanthopanax senticosus Harms on CYP2C9 Activity (Part 2) Tsunehisa TAKAHASHI, Takashi SATOH, Kazuhiro WATANABE 1 Hokkaido Pharmaceutical University School of Pharmacy 2 Amino Up Chemical Co., Ltd. Objective: Acanthopanax senticosus Harms extract (ASE) is an ingredient of functional foods, such as health supplements, in Japan. We investigated the effects of ASE on CYP2C9 activity. Methods and Results: CYP2C9-catalyzed diclofenac 4'-hydroxylase activities in human intestinal and liver microsomes (abbreviated as HIM and HLM, respectively) were significantly decreased by the addition of ASE in a concentration-dependent manner. Kinetic studies of diclofenac 4'-hydroxylase in HLM revealed that ASE addition significantly decreased Vmax but had no effect on Km. These results suggest that diclofenac 4'-hydroxylase activity is suppressed by ASE addition in a non-competitive manner. Then, we investigated the time courses of diclofenac 4'-hydroxylase activity in rat liver microsomes after ASE oral administration (50 to 400 mg/kg). Diclofenac 4'-hydroxylase activities were significantly lowered by the administration of 200 and 400 mg/kg ASE at 0.5 to 4 hr compared with control (0 hr). Furthermore, we investigated the effects of ASE oral administration on the pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats. The area under the concentration-time curve of tolbutamide after ASE oral administration (400 mg/kg) was enhanced by approximately 1.6 times compared with that without ASE oral administration. Conclusion: These findings indicated that ASE inhibits human intestinal and hepatic CYP2C9 activities.

Food and Drug Interactions: Effect of <i>Acanthopanax senticosus</i> Harms on CYP2C9 Activity (Part 2)