Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research
As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID‐19) today, arbidol often involves drug–drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography–tandem mas...
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| Format: | Article |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1292354/full |
| _version_ | 1797448465533370368 |
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| author | Jingjing Nie Jingjing Nie Hailun Xia Ya-Nan Liu Yige Yu Ren-Ai Xu |
| author_facet | Jingjing Nie Jingjing Nie Hailun Xia Ya-Nan Liu Yige Yu Ren-Ai Xu |
| author_sort | Jingjing Nie |
| collection | DOAJ |
| description | As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID‐19) today, arbidol often involves drug–drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 μL incubation system was used to study the inhibitory effect of the antitumor drug napabucasin on arbidol in vitro, with IC50 values of 2.25, 3.91, and 67.79 μM in rat liver microsomes (RLMs), human liver microsomes (HLMs), and CYP3A4.1, respectively. In addition, we found that the mechanism of inhibition was non-competitive inhibition in RLM and mixed inhibition in HLM. In pharmacokinetic experiments, it was observed that after gavage administration of 48 mg/kg napabucasin and 20 mg/kg arbidol, napabucasin inhibited the metabolism of arbidol in vivo and significantly changed the pharmacokinetic parameters of arbidol, such as AUC(0-t) and AUC(0-∞), in rats. We also found that napabucasin increased the AUC(0-t) and AUC(0-∞) of M6-1, the main metabolite of arbidol. This study provides a reference for the combined use of napabucasin and arbidol in clinical practice. |
| first_indexed | 2024-03-09T14:10:51Z |
| format | Article |
| id | doaj.art-6b95fff2c72944fbbd7ab0e4d71f6a6e |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-09T14:10:51Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-6b95fff2c72944fbbd7ab0e4d71f6a6e2023-11-29T11:34:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-11-011410.3389/fphar.2023.12923541292354Inhibitory effect of napabucasin on arbidol metabolism and its mechanism researchJingjing Nie0Jingjing Nie1Hailun Xia2Ya-Nan Liu3Yige Yu4Ren-Ai Xu5Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaAs a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID‐19) today, arbidol often involves drug–drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 μL incubation system was used to study the inhibitory effect of the antitumor drug napabucasin on arbidol in vitro, with IC50 values of 2.25, 3.91, and 67.79 μM in rat liver microsomes (RLMs), human liver microsomes (HLMs), and CYP3A4.1, respectively. In addition, we found that the mechanism of inhibition was non-competitive inhibition in RLM and mixed inhibition in HLM. In pharmacokinetic experiments, it was observed that after gavage administration of 48 mg/kg napabucasin and 20 mg/kg arbidol, napabucasin inhibited the metabolism of arbidol in vivo and significantly changed the pharmacokinetic parameters of arbidol, such as AUC(0-t) and AUC(0-∞), in rats. We also found that napabucasin increased the AUC(0-t) and AUC(0-∞) of M6-1, the main metabolite of arbidol. This study provides a reference for the combined use of napabucasin and arbidol in clinical practice.https://www.frontiersin.org/articles/10.3389/fphar.2023.1292354/fullarbidolnapabucasindrug–drug interactionsmetabolismCYP3A4 |
| spellingShingle | Jingjing Nie Jingjing Nie Hailun Xia Ya-Nan Liu Yige Yu Ren-Ai Xu Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research Frontiers in Pharmacology arbidol napabucasin drug–drug interactions metabolism CYP3A4 |
| title | Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research |
| title_full | Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research |
| title_fullStr | Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research |
| title_full_unstemmed | Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research |
| title_short | Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research |
| title_sort | inhibitory effect of napabucasin on arbidol metabolism and its mechanism research |
| topic | arbidol napabucasin drug–drug interactions metabolism CYP3A4 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1292354/full |
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