Favipiravir shows anti-influenza virus activities with IC50 ranged from 0.013 to 0.48 μg/ml for the influenza A viruses, from 0.039 to 0.089 μg/ml for the influenza B viruses, and from 0.030 to 0.057 μg/ml for the influenza C viruses. In mammalian cell lines (MDCK cells, Vero cells, HEL cells, A549 cells, HeLa cells, and HEp-2 cells), Favipiravir shows no cytotoxicity at concentrations up to 1,000 μg/ml. In MDCK cells inoculated with seasonal influenza A (H1N1) viruses, Favipiravir induces lethal mutagenesis.
| Cell Experiment | |
|---|---|
| Cell lines | MDCK cells, Vero cells, HEL cells, A549 cells, HeLa cells, and HEp-2 cells |
| Preparation method | The cytotoxicity of T-705 is evaluated by an assay with XTT. XTT is converted to aqueous formazan by an enzyme in MDCK cells, Vero cells, HEL cells, A549 cells, HeLa cells, and HEp-2 cells. The compounds are diluted to the appropriate concentrations (volume, 100 μl) with test medium (EMEM containing 10% FCS) in 96-well culture plates in which each well contains a concentration of 2 × 103 cells/100 μL. The test plates are incubated for 3 days at 37°C in 100% humidity and 5% CO2. After 3 days, 50 μl of the XTT reagent (1 mg/ml in FCS-free EMEM containing 5 mM phenazine methosulfate) is added, and the reaction product is assayed by measurement of the absorbance at 450 nm with a microplate reader. Cytotoxicity is expressed as the 50% cell-inhibitory concentration (CC50). |
| Concentrations | 1000 μg/mL |
| Incubation time | 3 d |
| Animal Experiment | |
|---|---|
| Animal models | Mice infected with influenza virus A/PR/8/34 |
| Formulation | 0.5% methylcellulose |
| Dosages | 200 mg/kg/day |
| Administration | p.o. |
| Molecular Weight | 157.1 |
| Formula | C5H4FN3O2 |
| CAS Number | 259793-96-9 |
| Solubility (25°C) | 31 mg/mL in DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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