Pharmacokinetic characterization of favipiravir in patients with COVID‐19

Abstract

This prospective observational study describes the pharmacokinetic characteristics of favipiravir in adult patients hospitalized for mild to moderate COVID‐19 with a positive RT‐PCR test. Favipiravir was administered for 5 days, with a loading dose of 3200 mg and a maintenance dose of 1200 mg/day. Serial blood samples were collected on Day 2 and Day 4 of the therapy. Laboratory findings of the patients (n = 21) and in‐hospital mortality were recorded. Favipiravir concentrations exhibited substantial variability and a significant decrease during the treatment of COVID‐19. The median favipiravir trough concentration (C0‐trough) on Day 2 was 21.26 (interquartile range [IQR], 8.37–30.78) μg/mL, whereas it decreased significantly to 1.61 (IQR, 0.00–6.41) μg/mL on Day 4, the area under the concentration–time curve decreased by 68.5%. Day 2 C0‐trough of female patients was higher than male patients. Our findings indicate that favipiravir concentrations show significant variability during the treatment of COVID‐19 and therapeutic drug monitoring may be necessary to maintain targeted concentrations.

Favipiravir treatment in non-severe COVID-19: promising results from multicenter propensity score-matched study (FAVICOV)

“…Based on PK data, the FPV trough concentration substantially decreased by 89% between day 2 (21.26 μg/mL) and day 4 (1.6 μg/mL) after COVID-19 treatment in Turkish, with the majority having BMI > 25 kg/m 2 and predicted to decrease over time, while, the plasma concentration need > 20 μg/mL to achieve the 50% effective concentration (EC50) value (9.4 μg/mL). However, the trough concentration in healthy volunteers ranged from 20 to 60 μg/mL (Day 1: 600 mg bid, day 2–5: 600 mg bid) 26 – 28 . The population PK study showed that body surface area, dosage, and invasive mechanical ventilation were related to clearance and bioavailability.…”

Does the Ethnic Difference Affect the Pharmacokinetics of Favipiravir? A Pharmacokinetic Study in Healthy Egyptian Volunteers and Development of Level C In-vitro In-vivo Correlation

“…The efficacy of favipiravir against several viral infections has emerged as possible therapy for COVID-19 [29]. The pharmacokinetic profile of favipiravir is quite complex [30]. Inconsistency in the efficacy outcomes of favipiravir treatment in many clinical studies can be attributed to a variety of factors, including research design, demographic, and ethnicity [31].…”

Safety and efficacy of four drug regimens versus standard-of-care for the treatment of symptomatic outpatients with COVID-19: A randomised, open-label, multi-arm, phase 2 clinical trial

“…Additionally, FPV pharmacokinetics display high variability in COVID-19 patients, and higher doses may be necessary. 38 Similarly, for the NTZ component, we used a dose of 1000 mg BID with food, whereas recent pharmacokinetic modelling predicts an optimal dose of 1400 mg BID with food. 39 The FPV + NTZ arm had the highest frequency of adverse events in this study, though in healthy volunteers NTZ doses of up to 1500 mg are well tolerated.…”