Table 5.
Pharmacokinetic parameters of molnupiravir and NHC in the rat blood and brain after treatment with molnupiravir (100 mg/kg, i.v.) alone, molnupiravir (100 mg/kg, i.v.) + BNPP (50 mg/kg, i.v.), or molnupiravir (100 mg/kg, i.v.) + the herbal extract Scutellaria formula-NRICM101 (1.27 g/kg, p.o.).
| Parameter | Molnupiravir (100 mg/kg, i.v.) |
|||
|---|---|---|---|---|
| Blood |
Brain |
|||
| Molnupiravir | NHC | Molnupiravir | NHC | |
| AUC (min μg/mL) | 3432 ± 397.1b | 8025 ± 652.7 | 19.07 ± 3.62b | 64.68 ± 6.90 |
| Cmax (μg/mL) | 191.5 ± 24.11 | 153.9 ± 8.15b | 0.39 ± 0.10 | 0.65 ± 0.03 |
| t1/2 (min) | 9 ± 2b | 88 ± 14 | 10 ± 1b | 84 ± 21c |
| Tmax (min) | - | 40 | 40 | 43 ± 7 |
| CL (mL/min/kg) | 32.07 ± 4.45 | - | - | - |
| MRT (min) | 18 ± 2b | 66 ± 1b | 35 ± 1b | 102 ± 14c |
| AUCNHC/AUCmolnupiravir | - | 2.33 ± 0.19b | - | 4.77 ± 0.87 |
| AUCbrain/AUCblood | - | - | 0.005 ± 0.001b | 0.008 ± 0.0003 |
| Molnupiravir (100 mg/kg, i.v.) + BNPP (50 mg/kg, i.v.) | ||||
| AUC (min μg/mL) | 6578 ± 667.6a | 3476 ± 157.9a | 107.43 ± 23.45a | 195.2 ± 47.67a |
| Cmax (μg/mL) | 199.4 ± 16.95 | 39.84 ± 4.0a | 0.79 ± 0.22 | 1.28 ± 0.34 |
| t1/2 (min) | 132 ± 32a | 104 ± 14 | 148 ± 34a | 105 ± 14c |
| Tmax (min) | - | 40 | 40 | 40 |
| CL (mL/min/kg) | 15.96 ± 1.28 | - | - | - |
| MRT (min) | 77 ± 16a | 89.65 ± 3.19 | 238 ± 56 | 176 ± 24c |
| AUCNHC/AUCmolnupiravir | - | 0.53 ± 0.02a | - | 1.82 ± 0.44 |
| AUCbrain/AUCblood | - | - | 0.02 ± 0.004a | 0.06 ± 0.01a |
| AUCmolnupiravir+ BNPP/AUCmolnupiravir | 1.92 ± 0.19 | 0.49 ± 0.04 | 5.63 ± 1.23 | 3.02 ± 0.74 |
| Molnupiravir (100 mg/kg, i.v.) + the Scutellaria formula-NRICM101 (1.27 g/kg, p.o.) | ||||
| AUC (min μg/mL) | 4645 ± 151.7b | 3776 ± 246.4a | 45.27 ± 11.92 | 232.2 ± 16.68a |
| Cmax (μg/mL) | 184.7 ± 18.66 | 71.24 ± 2.98a,b | 0.50 ± 0.09 | 1.13 ± 0.33 |
| t1/2 (min) | 35 ± 10b | 189 ± 45 | 68 ± 22 | 386 ± 57a,b |
| Tmax (min) | - | 40 | 40 | 50 ± 4 |
| CL (mL/min/kg) | 21.66 ± 0.66 | - | - | - |
| MRT (min) | 29 ± 7b | 73 ± 3b | 53 ± 15b | 445 ± 64b |
| AUCNHC/AUCmolnupiravir | - | 0.83 ± 0.06a | - | 5.13 ± 0.37 |
| AUCbrain/AUCblood | - | - | 0.01 ± 0.003 | 0.06 ± 0.004a |
| AUCmolnupiravir+ Herbs/AUCmolnupiravir | 1.35 ± 0.04 | 0.47 ± 0.03 | 2.37 ± 0.63 | 3.59 ± 0.26 |
Abbreviations: AUC, area under curve the concentration-time curve; t1/2, half-life; Cmax, concentration maximum; CL, clearance; MRT, mean residence time; Herbs, the extract of the Scutellaria formula-NRICM101 (1.27 g/kg, p.o., for five consecutive days).
AUCbrain/AUCblood represents the rat blood-to-brain transfer ratio. Data have been expressed as the mean ± SEM (n = 6).
ap < 0.05 compared with the molnupiravir (100 mg/kg, i.v.) alone group by one-way ANOVA with post hoc Tukey HSD test.
bp < 0.05 compared with the molnupiravir (100 mg/kg, i.v.) + BNPP (50 mg/kg, i.v.) group by one-way ANOVA with post hoc Tukey HSD test.
cp < 0.05 compared with the molnupiravir (100 mg/kg, i.v.) + the herbal extract Scutellaria formula-NRICM101 (1.27 g/kg, p.o.) group by one-way ANOVA with post hoc Tukey HSD test.