Inhibition of CYP3A-mediated Midazolam Metabolism by Kaempferia Parviflora .

Autor:	Kashiwabuchi Y; Department of Pharmacology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan., Nishimura Y; Department of Pharmacology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan., Kurata N; Department of Pharmacology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan., Iwase M; Department of Pharmacology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan., Kiuchi Y; Department of Pharmacology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan., Nobe K; Department of Pharmacology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Jazyk:	angličtina
Zdroj:	Food safety (Tokyo, Japan) [Food Saf (Tokyo)] 2022 Mar 03; Vol. 10 (1), pp. 32-41. Date of Electronic Publication: 2022 Mar 03 (Print Publication: 2022).
DOI:	10.14252/foodsafetyfscj.D-21-00013
Abstrakt:	Kaempferia parviflora (KP) extract has recently attracted attention in Japan as a dietary supplement; however, there is little information regarding food-drug interactions (FDIs). The current study was conducted to clarify the FDI of KP extract via inhibition of cytochrome P450 3A (CYP3A), a typical drug-metabolizing enzyme. The inhibitory effects of KP extract and its main ingredients, 5,7-dimethoxyflavone (5,7-DMF) and 3,5,7,3',4'-pentamethoxyflavone (3,5,7,3',4'-PMF), on CYP3A-mediated midazolam 1'-hydroxylation (MDZ 1'-OH) activity were investigated in human liver microsomes. In addition, the effect of a single oral treatment with KP extract (135 mg/kg) on oral MDZ (15 mg/kg) metabolism was investigated in rats. Serum MDZ concentration was analyzed and pharmacokinetic parameters were compared with the control group. KP extract competitively inhibited MDZ 1'-OH activity with an inhibition constant value of 78.14 µg/ml, which was lower than the estimated concentration in the small intestine after ingestion. Furthermore, KP extract, 5,7-DMF, and 3,5,7,3',4'-PMF inhibited the activity in a time-, NADPH-, and concentration-dependent manner. In vivo study showed that administration of KP extract to rats 2 h before MDZ significantly increased the area under the serum concentration-time curve and the maximum concentration of MDZ significantly by 2.3- and 1.9- fold, respectively ( p < 0.05). Conversely, administration of MDZ 18 h after KP extract treatment displayed a weaker effect. These results suggest that KP extract competitively inhibits CYP3A-mediated MDZ metabolism, and that this inhibition may be time-dependent but not irreversible. This work suggests an FDI through CYP3A inhibition by KP extract. Competing Interests: Conflict of Interest: The authors have no conflict of interest. (©2022 Food Safety Commission, Cabinet Office, Government of Japan.)
Databáze:	MEDLINE
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