The Relationship Between Plasma Favipiravir Concentrations and Clinical Outcomes in COVID-19

Question addressed by the study Favipiravir has shown efficacy against SARS-CoV-2 in patients under 60, but data linking plasma concentrations to clinical outcomes are limited. This study investigated whether favipiravir plasma concentrations influence clinical efficacy and outcomes in hospitalised COVID-19 patients and asked: how can antiviral dosing strategies be optimised to improve pandemic preparedness and treatment efficacy? Materials/patients and methods Adult participants were drawn from the PIONEER trial, in which patients received oral favipiravir (1800 mg twice daily on day 1, then 800 mg twice daily for nine days) plus standard care. This analysis included patients with confirmed COVID-19 and ≥75% study adherence. Samples were collected between days 5–10 post-treatment initiation. The primary outcome was time to clinical improvement. Secondary outcomes included achievement of clinical improvement and mortality risk. Results Of 140 patients (50% male; mean age 59.5 [ sd 14.8]), 29 (21%) reached target plasma concentrations. Mean time to improvement was 7.7 [5.9] vs 9.1 [7.2] days for target achievers vs non-achievers (p=0.26). Target was more often achieved in females (34%) than males (7%) (p=0.0002). Plasma concentration inversely correlated with BMI (r=–0.4; p<0.0001), with lower BMI in achievers (26.0 [5.1] vs 30.5 [6.9]; p=0.003). ALP and ALT levels were also lower in achievers (p=0.004 and p=0.02, respectively). Answer to the question Most patients did not reach target favipiravir levels. Concentrations were influenced by sex, BMI, and liver function, confirming the need for pharmacokinetically guided dosing and therapeutic monitoring to optimise antiviral efficacy in future pandemic responses.