The relationship between plasma favipiravir concentrations and clinical outcomes in COVID-19

Favipiravir has shown efficacy against SARS-CoV-2 in patients <60 years old, but data linking plasma concentrations to clinical outcomes are limited. This study investigated whether favipiravir plasma concentrations influence clinical efficacy and outcomes in patients hospitalised with COVID-19. The main research question was, How can antiviral dosing strategies be optimised to improve pandemic preparedness and treatment efficacy?

Adult participants were drawn from the PIONEER trial, in which patients received oral favipiravir (1800 mg twice daily for 1 day, then 800 mg twice daily for 9 days) plus standard care. This analysis included patients with confirmed COVID-19 and ≥75% study adherence. Samples were collected between days 5 and 10 post-treatment initiation. The primary outcome was time to clinical improvement. Secondary outcomes included achievement of clinical improvement and mortality risk.

Out of 140 patients (50% male; mean±sd age 59.5±14.8 years), target plasma concentrations were reached in 29 (21%). Mean time to improvement was 7.7±5.9 days in target achievers versus 9.1±7.2 days in non-achievers (p=0.26). The target was more often achieved in female (34%) than male (7%) participants (p=0.0002). Plasma concentration inversely correlated with body mass index (r= -0.4, p<0.0001), and with lower body mass index in achievers (26.0±5.1 kg·m^-2 versus 30.5±6.9 kg·m^-2, p=0.003). Alkaline phosphatase and alanine aminotransferase levels were also lower in achievers (p=0.004 and p=0.02, respectively).

Most patients did not reach target favipiravir levels. Concentrations were influenced by sex, body mass index and liver function, confirming the need for pharmacokinetically guided dosing and therapeutic monitoring to optimise antiviral efficacy in future pandemic responses.