Future of antivirals in COVID-19: The case of favipiravir

Kow, Chia Siang; Ramachandram, Dinesh Sangarran; Hasan, Syed Shahzad

doi:10.1016/j.intimp.2021.108455

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…However, recent study showed a lack of positive effect of FPV on mortality, that could be attributed to the low plasma concentrations of FPV following oral administration 6 . Some adverse effects were noted with FPV such as diarrhea, changes in liver function parameters and hyperuricemia 7 .…”

Section: Introductionmentioning

confidence: 99%

A solvent-free HPLC method for the simultaneous determination of Favipiravir and its hydrolytic degradation product

Sharaf,

Abd El-Fattah,

El-Sayed

et al. 2023

Sci Rep

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During COVID-19 pandemic, Favipiravir (FPV) showed a great efficacy against COVID-19 virus, it produced noticeable improvements in recovery of the patients. The aim of this study was to develop a new, green and simple method for the simultaneous determination of FPV and its acid-induced degradation product (ADP) in its pure and pharmaceutical dosage forms. This method will be key for the inevitable development of FPV solution and inhaler formulations. A green micellar RP-HPLC method was developed using an RP-VDSPHERE PUR 100 column (5 µm, 250 × 4.6 mm) and an isocratic mixed micellar mobile phase composed of 0.02 M Brij-35, 0.1 M SDS and 0.01 M potassium dihydrogen orthophosphate anhydrous and adjusted to pH 3.0 with 1.0 mL min−1 flow rate. The detection was performed at 280 nm with a run time of less than six min. Under the optimized chromatographic conditions, linear relationship has been established between peak area and concentration of FPV and its ADP in the range of 5–100 and 10–100 µg mL−1 with elution time of 3.8 and 5.7 min, respectively. The developed method was validated according to the ICH guidelines and applied successfully for determination of FPV in its pharmaceutical dosage form.

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Section: Introductionmentioning

confidence: 99%

A solvent-free HPLC method for the simultaneous determination of Favipiravir and its hydrolytic degradation product

Sharaf,

Abd El-Fattah,

El-Sayed

et al. 2023

Sci Rep

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“…The dosing regimen for patients with COVID-19 according to the Japanese Association for Infectious Diseases is 3600 mg (18 tablets/day) on the first day and 1600 mg (8 tablets/day) from second day onward, for up to 14 days (Joshi et al, 2021 ). However, a recent meta-analysis of clinical trials revealed no significant difference between the mortality rates of patients with COVID-19 treated with favipiravir and those not treated with favipiravir (Kow et al, 2022 ). Authors have underlined that the lack of beneficial effect of favipiravir treatment on mortality could be associated with the complex pharmacokinetic profile of the orally administered favipiravir, leading to low plasma concentrations (Kow et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…However, a recent meta-analysis of clinical trials revealed no significant difference between the mortality rates of patients with COVID-19 treated with favipiravir and those not treated with favipiravir (Kow et al, 2022 ). Authors have underlined that the lack of beneficial effect of favipiravir treatment on mortality could be associated with the complex pharmacokinetic profile of the orally administered favipiravir, leading to low plasma concentrations (Kow et al, 2022 ). Accordingly, lung targeting through inhalation of favipiravir is not only expected to overcome the low bioavailability of oral administration, but also aims to achieve a higher drug concentration in the lung tissues.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary delivery of favipiravir inhalation solution for COVID-19 treatment: in vitro characterization, stability, in vitro cytotoxicity, and antiviral activity using real time cell analysis

et al. 2022

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Favipiravir, an RNA-dependent RNA polymerase (RdRp) inhibitor, is used to treat patients infected with influenza virus and most recently with SARS-CoV-2. However, poor accumulation of favipiravir in lung tissue following oral administration has required an alternative method of administration that directly targets the lungs. In this study, an inhalation solution of favipiravir at a concentration of 2 mg mL −1 was developed and characterized for the first time. The chemical stability of inhaled favipiravir solution in two different media, phosphate buffer saline (PBS) and normal saline (NS), was investigated under different conditions: 5 ± 3 °C, 25 ± 2 °C/60% RH ± 5% RH, and 40 ± 2 °C/75% RH ± 5% RH; in addition to constant light exposure. As a result, favipiravir solution in PBS revealed superior stability over 12 months at 5 ± 3 °C. Antiviral activity of favipiravir was assessed at the concentrations between 0.25 and 3 mg mL −1 with real time cell analyzer on Vero-E6 that were infected with SARS-CoV-2/B.1.36. The optimum concentration was found to be 2 mg mL −1 , where minimum toxicity and sufficient antiviral activity was observed. Furthermore, cell viability assay against Calu-3 lung epithelial cells confirmed the biocompatibility of favipiravir at concentrations up to 50 μM (7.855 mg mL −1 ). The in vitro aerodynamic profiles of the developed inhaled favipiravir formulation, when delivered with soft-mist inhaler indicated good lung targeting properties. These results suggest that favipiravir solution prepared with PBS could be considered as a suitable and promising inhalation formulation for pulmonary delivery in the treatment of patients with COVID-19.

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“…The analysis showed that using favipiravir is associated with a reduced 28-day mortality risk in patients with severe COVID-19. However, prior to the reporting of this analysis, the randomised evidence 2 showed no mortality benefits with the use of favipiravir among patients with COVID-19, and thus there has been little enthusiasm for investigating this antiviral agent. For instance, the recent randomised trial by Shah and colleagues 3 observed no significant difference in the mortality rate between favipiravir group and standard care group (26 [10%] of 251 patients in the favipiravir group versus 34 [14%] of 248 patients in the standard care group; hazard ratio = 0.74 [95% confidence interval 0.44–1.23]).…”

mentioning

confidence: 99%

Favipiravir and hyperuricemia in patients with COVID-19—suggestions for future studies

Kow,

Ramachandram,

Hasan

2023

The Lancet Regional Health - Southeast Asia

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Future of antivirals in COVID-19: The case of favipiravir

Cited by 5 publications

References 7 publications

A solvent-free HPLC method for the simultaneous determination of Favipiravir and its hydrolytic degradation product

A solvent-free HPLC method for the simultaneous determination of Favipiravir and its hydrolytic degradation product

Pulmonary delivery of favipiravir inhalation solution for COVID-19 treatment: in vitro characterization, stability, in vitro cytotoxicity, and antiviral activity using real time cell analysis

Favipiravir and hyperuricemia in patients with COVID-19—suggestions for future studies

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