| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2024-03-21 |
| タイトル |
|
|
タイトル |
Mechanism Underlying Conflicting Drug-Drug Interaction Between Aprepitant and Voriconazole via Cytochrome P450 3A4-Mediated Metabolism |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
言語 |
en |
|
主題 |
aprepitant |
| キーワード |
|
|
言語 |
en |
|
主題 |
CYP3A4 |
| キーワード |
|
|
言語 |
en |
|
主題 |
drug interaction |
| キーワード |
|
|
言語 |
en |
|
主題 |
L-755446 |
| キーワード |
|
|
言語 |
en |
|
主題 |
voriconazole |
| 資源タイプ |
|
|
資源タイプ |
journal article |
| アクセス権 |
|
|
アクセス権 |
open access |
| 著者 |
Ishida,Masako
Kumagai,Takeshi
Yamamoto,Tatsuro
Suzuki,Hiroyuki
Moriki,Kuniaki
Fujiyoshi,Masachika
Nagata,Kiyoshi
島田,美樹
|
| 著者所属（英） |
|
|
値 |
Department of Pharmacy, Tottori University Hospital |
| 著者所属（英） |
|
|
値 |
Laboratory of Environmental and Health Sciences, Tohoku Medical and Pharmaceutical University |
| 著者所属（英） |
|
|
値 |
Department of Pharmacy, Tottori University Hospital |
| 著者所属（英） |
|
|
値 |
Division of Clinical Pharmaceutics, Tohoku Medical and Pharmaceutical University |
| 著者所属（英） |
|
|
値 |
Department of Pharmacy, Tottori University Hospital |
| 著者所属（英） |
|
|
値 |
Department of Pharmacy, Tottori University Hospital |
| 著者所属（英） |
|
|
値 |
Laboratory of Environmental and Health Sciences, Tohoku Medical and Pharmaceutical University |
| 著者所属（英） |
|
|
言語 |
en |
|
値 |
Department of Pharmacy, Tottori University Hospital |
| 抄録 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
Background: Voriconazole is an antifungal drug for which therapeutic monitoring is recommended to prevent side effects. Temporary administration of the antiemetic drug fosaprepitant remarkably decreases the plasma concentration of voriconazole from the therapeutic range. The ratio of the major metabolite voriconazole N-oxide to voriconazole exceeded that at any other time for a patient who started chemotherapy during voriconazole therapy. We attributed this unpredictable result to cytochrome P450 3A4 induced by aprepitant that was converted from fosaprepitant in vivo. Methods: Concentrations of voriconazole and voriconazole N-oxide were measured using liquid chromatography-mass spectrometry/mass spectrometry in primary human hepatocytes after incubation with aprepitant. Aprepitant suppressed voriconazole N-oxide formation within 24 h, followed by a continuous increase. Levels of drug-metabolizing cytochrome P450 mRNA were measured using real-time PCR in primary human hepatocytes incubated with aprepitant. Results: Cytochrome P450 3A4 and 2C9 mRNA levels increased ~4- and 2-fold, respectively, over time. Cytochrome P450 3A4 induction was confirmed using reporter assays. We also assessed L-755446, a major metabolite of aprepitant that lacks a triazole ring. Both compounds dose-dependently increased reporter activity; however, induction by L-755446 was stronger than that by aprepitant. Conclusion: These results indicate that aprepitant initially inhibited voriconazole metabolism via its triazole ring and increased cytochrome P450 3A4 induction following L-755446 formation. The decrease in plasma voriconazole concentration 7 days after fosaprepitant administration was mainly attributed to cytochrome P450 3A4 induction by L-755446. |
|
言語 |
en |
| 書誌情報 |
en : Yonago Acta Medica
巻 67,
号 1,
p. 31-40,
ページ数 10,
発行日 2024-02-21
|
| 出版者 |
|
|
出版者 |
Tottori University Medical Press |
|
言語 |
en |
| ISSN |
|
|
収録物識別子タイプ |
PISSN |
|
収録物識別子 |
13468049 |
| 書誌レコードID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA00892882 |
| 権利 |
|
|
言語 |
en |
|
権利情報 |
(C)2024 Tottori University Medical Press |
| 情報源 |
|
|
|
関連名称 |
Yonago Acta Medica. 2024, 67(1), 31-40. |
| 関連サイト |
|
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|
識別子タイプ |
URI |
|
|
関連識別子 |
https://www.lib.tottori-u.ac.jp/yam/yam/yam67-1/67-1contents.html |
|
|
関連名称 |
https://www.lib.tottori-u.ac.jp/yam/yam/yam67-1/67-1contents.html |
| 関連サイト |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.33160/yam.2024.02.004 |
|
|
関連名称 |
https://doi.org/10.33160/yam.2024.02.004 |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
yam67(1)_31.pdf
