Oral Favipiravir Exposure and Pharmacodynamic Effects in Outpatient Adults with Acute Influenza.
J Infect Dis
; 2023 Sep 22.
Article
en En
| MEDLINE
| ID: mdl-37739792
ABSTRACT
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 (1800â mg BID on day 1, 800â 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 >80â 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Clinical_trials
Idioma:
En
Revista:
J Infect Dis
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos