Oral Favipiravir Exposure and Pharmacodynamic Effects in Outpatient Adults with Acute Influenza
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America..
BACKGROUND: The pharmacokinetics of oral favipiravir and the relationships of plasma concentrations to antiviral effects are incompletely studied in influenza.
METHODS: Serial plasma samples were collected from adults with uncomplicated influenza who were randomized to favipiravir (1800 mg BID on day 1, 800 mg BID on days 2 to 5)(N = 827) or placebo (N = 419) in two phase 3 trials. Post hoc analyses assessed the frequency of reaching an average Cmin ≥20ug/ml, its association with antiviral efficacy, and factors associated with reduced favipiravir exposure.
RESULTS: Wide inter-individual variability existed in favipiravir concentrations, and this regimen failed to reach an average Cmin >20ug/ml in 41-43% of participants. Those attaining this threshold showed greater reductions in nasopharyngeal infectious virus titers on treatment days 2 and 3 (approximately 0.3-0.4 log10TCID50/ml) and lower viral titer AUCs compared to those who did not. Those with average Cmin <20ug/ml had over 2-fold higher mean ratios of the metabolite T-705-M1 to favipiravir, consistent with greater metabolism, and were more likely to weigh >80 kg (61.5-64%).
CONCLUSIONS: Higher favipiravir levels with average Cmin >20ug/ml were associated with larger antiviral effects and more rapid illness alleviation compared to placebo and to favipiravir recipients with lower average Cmin values in uncomplicated influenza.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
The Journal of infectious diseases - (2023) vom: 22. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hayden, Frederick G [VerfasserIn] |
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| Links: |
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| Themen: |
Antiviral effects |
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| Anmerkungen: |
Date Revised 22.09.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1093/infdis/jiad409 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36236298X |
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| 100 | 1 | |a Hayden, Frederick G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Oral Favipiravir Exposure and Pharmacodynamic Effects in Outpatient Adults with Acute Influenza |
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| 500 | |a Citation Status Publisher | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. | ||
| 520 | |a BACKGROUND: The pharmacokinetics of oral favipiravir and the relationships of plasma concentrations to antiviral effects are incompletely studied in influenza | ||
| 520 | |a METHODS: Serial plasma samples were collected from adults with uncomplicated influenza who were randomized to favipiravir (1800 mg BID on day 1, 800 mg BID on days 2 to 5)(N = 827) or placebo (N = 419) in two phase 3 trials. Post hoc analyses assessed the frequency of reaching an average Cmin ≥20ug/ml, its association with antiviral efficacy, and factors associated with reduced favipiravir exposure | ||
| 520 | |a RESULTS: Wide inter-individual variability existed in favipiravir concentrations, and this regimen failed to reach an average Cmin >20ug/ml in 41-43% of participants. Those attaining this threshold showed greater reductions in nasopharyngeal infectious virus titers on treatment days 2 and 3 (approximately 0.3-0.4 log10TCID50/ml) and lower viral titer AUCs compared to those who did not. Those with average Cmin <20ug/ml had over 2-fold higher mean ratios of the metabolite T-705-M1 to favipiravir, consistent with greater metabolism, and were more likely to weigh >80 kg (61.5-64%) | ||
| 520 | |a CONCLUSIONS: Higher favipiravir levels with average Cmin >20ug/ml were associated with larger antiviral effects and more rapid illness alleviation compared to placebo and to favipiravir recipients with lower average Cmin values in uncomplicated influenza | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a favipiravir | |
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| 650 | 4 | |a pharmacokinetics | |
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| 700 | 1 | |a Epstein, Carol |e verfasserin |4 aut | |
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