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Inhibitory Effect of Polypodium Leucotomos Extract on Cytochrome P450 3A-mediated Midazolam Metabolism
https://showa.repo.nii.ac.jp/records/2988
https://showa.repo.nii.ac.jp/records/298809311c67-4056-47db-a72f-dfc542a2e006
名前 / ファイル | ライセンス | アクション |
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S31_29.pdf (780.0 kB)
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Item type | 学内発行雑誌 / Departmental Bulletin Paper(1) | |||||
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公開日 | 2019-08-09 | |||||
タイトル | ||||||
タイトル | Inhibitory Effect of Polypodium Leucotomos Extract on Cytochrome P450 3A-mediated Midazolam Metabolism | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ | departmental bulletin paper | |||||
著者 |
GOMI, Yurika
× GOMI, Yurika× NISHIMURA, Yuki× KURATA, Norimitsu× IWASE Mariko× SHINYA, Koichiro× KIUCHI, Yuji |
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書誌情報 |
The Showa University journal of medical sciences 巻 31, 号 1, p. 29-39, 発行日 2019-03 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Polypodium leucotomos(PL)is a fern native to Latin America, and its extract is used as an oral sunscreen; however, its safety during use has not been adequately investigated. Therefore, the aim of this study was to evaluate food-drug interactions associated with PL extract mediated by cytochrome P450 3A(CYP3A)inhibition and induction. Inhibition of CYP3A-mediated midazolam(MDZ)1’-hydroxylation activity by PL extract and its major phenolic components was evaluated in vitro using pooled human liver microsomes. In addition, MDZ pharmacokinetics were investigated in rats after a single dose, as well as after 1 week treatment with PL extract(30mg/kg)in order to evaluate the inhibitory and inducible effects of PL on CYP3A in vivo, respectively. Serum MDZ concentrations were analyzed and pharmacokinetic parameters were compared between PL- and water(control)-treated groups. In vitro, PL extract decreased MDZ 1’-hydroxylation activity in a concentration-dependent manner. However, the major phenolic compounds in PL extracts, namely caffeic, chlorogenic, p-coumaric, ferulic, and vanillic acids, did not exhibit any marked inhibitory effects on MDZ 1’-hydroxylation activity. In vivo, administration of a single dose of PL extract to rats significantly increased the area under the serum concentration-time curve from time 0 to infinity(AUC0–∞)and the maximum serum concentration(Cmax)of MDZ(by 57% and 88%, respectively; P<0.05). In contrast, there were no significant changes in MDZ pharmacokinetic parameters after 1 week of treatment with PL extract. These results suggest that PL extract can cause a food-drug interaction by inhibiting CYP3A. | |||||
DOI | ||||||
関連識別子 | 10.15369/sujms.31.29 | |||||
出版者 | ||||||
出版者 | Showa University Society | |||||
ISSN | ||||||
収録物識別子 | 0915-6380 | |||||
著者版フラグ | ||||||
出版タイプ | VoR |