Effect of the active ingredient of Kaempferia parviflora, 5,7-dimethoxyflavone, on the pharmacokinetics of midazolam

Wataru Ochiai; Hiroko Kobayashi; Satoshi Kitaoka; Mayumi Kashiwada; Yuya Koyama; Saho Nakaishi; Tomomi Nagai; Masaki Aburada; Kiyoshi Sugiyama

doi:10.1007/s11418-018-1184-z

Effect of the active ingredient of Kaempferia parviflora, 5,7-dimethoxyflavone, on the pharmacokinetics of midazolam

J Nat Med. 2018 Jun;72(3):607-614. doi: 10.1007/s11418-018-1184-z. Epub 2018 Mar 17.

Authors

Wataru Ochiai¹, Hiroko Kobayashi², Satoshi Kitaoka², Mayumi Kashiwada², Yuya Koyama², Saho Nakaishi², Tomomi Nagai², Masaki Aburada³, Kiyoshi Sugiyama⁴

Affiliations

¹ Department of Clinical Pharmacokinetics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan. w-ochiai@hoshi.ac.jp.
² Department of Clinical Pharmacokinetics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
³ Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan.
⁴ Department of Functional Molecule, Kinetics Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan. sugiyama@hoshi.ac.jp.

PMID: 29550915
DOI: 10.1007/s11418-018-1184-z

Abstract

5,7-Dimethoxyflavone (5,7-DMF), one of the major components of Kaempferia parviflora, has anti-obesity, anti-inflammatory, and antineoplastic effects. On the other hand, in vitro studies have reported that it directly inhibits the drug metabolizing enzyme family cytochrome P450 (CYP) 3As. In this study, its safety was evaluated from a pharmacokinetic point of view, based on daily ingestion of 5,7-DMF. Midazolam, a substrate of CYP3As, was orally administered to mice treated with 5,7-DMF for 10 days, and its pharmacokinetic properties were investigated. In the group administered 5,7-DMF, the area under the curve (AUC) of midazolam increased by 130% and its biological half-life was extended by approximately 100 min compared to the control group. Compared to the control group, 5,7-DMF markedly decreased the expression of CYP3A11 and CYP3A25 in the liver. These results suggest that continued ingestion of 5,7-DMF decreases the expression of CYP3As in the liver, consequently increasing the blood concentrations of drugs metabolized by CYP3As.

Keywords: 5,7-Dimethoxyflavone; CYP3As; Cytochrome P450; Kaempferia parviflora; Midazolam; Pharmacokinetics.

MeSH terms

Animals
Flavonoids / pharmacology
Flavonoids / therapeutic use*
Humans
Male
Mice
Midazolam / pharmacokinetics
Midazolam / therapeutic use*

Substances

Flavonoids
5,7-dimethoxyflavone
Midazolam