التفاصيل البيبلوغرافية
| العنوان: |
In Vivo Antiviral Activity of Baloxavir against PA/I38T-Substituted Influenza A Viruses at Clinically Relevant Doses |
| المؤلفون: |
Takayuki Kuroda, Keita Fukao, Shinpei Yoshida, Ryoko Oka, Kaoru Baba, Yoshinori Ando, Keiichi Taniguchi, Takeshi Noshi, Takao Shishido |
| المصدر: |
Viruses, Vol 15, Iss 5, p 1154 (2023) |
| بيانات النشر: |
MDPI AG, 2023. |
| سنة النشر: |
2023 |
| المجموعة: |
LCC:Microbiology |
| مصطلحات موضوعية: |
baloxavir, oseltamivir, influenza, PA/I38T, antiviral drugs, Microbiology, QR1-502 |
| الوصف: |
Although the prevalence of polymerase acidic (PA)/I38T strains of influenza virus with reduced susceptibility to baloxavir acid is low, there is a possibility of emergence under selective pressure. Furthermore, the virus may be transmitted between humans. We investigated the in vivo efficacy of baloxavir acid and oseltamivir phosphate against influenza A subtypes H1N1, H1N1pdm09, and H3N2, with PA/I38T substitution, at doses simulating human plasma concentrations. A pharmacokinetic/pharmacodynamic analysis was performed to strengthen the validity of the findings and the applicability in a clinical setting. Although the antiviral effect of baloxavir acid was attenuated in mice infected with PA/I38T-substituted viral strains compared with the wild type (WT), baloxavir acid significantly reduced virus titers at higher—but clinically relevant—doses. The virus titer reduction with baloxavir acid (30 mg/kg subcutaneous single dose) was comparable to that of oseltamivir phosphate (5 mg/kg orally twice daily) against H1N1 and H1N1pdm09 PA/I38T strains in mice, as well as the H3N2 PA/I38T strain in hamsters. Baloxavir acid demonstrated an antiviral effect against PA/I38T-substituted strains, at day 6, with no further viral rebound. In conclusion, baloxavir acid demonstrated dose-dependent antiviral effects comparable to that of oseltamivir phosphate, even though the degree of lung virus titer reduction was diminished in animal models infected with PA/I38T-substituted strains. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1999-4915 |
| Relation: |
https://www.mdpi.com/1999-4915/15/5/1154; https://doaj.org/toc/1999-4915 |
| DOI: |
10.3390/v15051154 |
| URL الوصول: |
https://doaj.org/article/10d935ba69ee4c45b0ca89d03f84d577 |
| رقم الانضمام: |
edsdoj.10d935ba69ee4c45b0ca89d03f84d577 |
| قاعدة البيانات: |
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