Food and Drug Interactions: Effect of Acanthopanax senticosus Harms on CYP2C9 Activity (Part 2)
10.1625/jcam.11.9
- VernacularTitle:食―薬間相互作用：薬物代謝酵素 (CYP2C9) 活性に対するエゾウコギの影響（第 2 報）
- Author:
Tsunehisa TAKAHASHI
;
Takashi SATOH
;
Kazuhiro WATANABE
- Publication Type:Journal Article
- Keywords:
Acanthopanax senticosus Harms;
CYP2C9;
food and drug interaction;
pharmacokinetics
- From:Japanese Journal of Complementary and Alternative Medicine
2014;11(1):9-15
- CountryJapan
- Language:Japanese
-
Abstract:
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.
