Leritrelvir (RAY1216 (150-600 mg/kg/day; i.g.; 5 days) effectively prolongs survival of SARS-CoV-2 infected mice[1].
Compound pharmacokinetics parameters in different animal species[1]
| Compound | Species | dose (mg/kg) | Cmax (nM) | Tmax (h) | AUC(0-last) (nM h) | Cl (mL/min/kg) | Vdss (L/kg) | T1/2 (h) | oral F (%) |
| Mouse | 3.0 (IV) | - | - | 7789 | 10 | 1.4 | 3.8 | - |
| | 10 (PO) | 1287 | 2.0 | 5698 | - | - | 2.6 | 22 |
| RAY1216 | rat | 2.0 (IV) | - | - | 4505 | 12.5 | 1.1 | 2.2 | - |
| | 10 (PO) | 916 | 0.9 | 7429 | - | - | 4.3 | 33 |
| cynomolgus macaque | 1.0 (IV) | - | - | 1157 | 22.5 | 1.0 | 0.9 | - |
| | 5.0 (PO) | 102 | 1.5 | 458 | - | - | 14.9 | 8 |
C
max: the maximum observed concentration of the drug collected in bodily material from subjects in a clinical study
T
max: the time it takes to reach the maximum concentration or time to C
max AUC: "Area Under the Curve” and represents the total exposure of the drug experienced by the subject in a clinical study
Cl: total plasma clearance
Vd
ss: Steady state volume of distribution
T
1/2: Half-time is the time it takes for half the drug concentration to be eliminated
oral (F%): Oral bioavailability
| Animal Model: | Female human ACE2 transgenic C57BL/6 mouse, SARS-CoV-2 infection model[1] |
| Dosage: | 150, 300 and 600 mg/kg/day |
| Administration: | Intragastric administration, 5 days |
| Result: | Protected mice infected with SARS-CoV-2 by 100%, 43% and 14% at 600, 300 and 150 mg/kg, respectively. Decreased viral titres in lungs significantly compared with the infection-only group. Reduced virus induced pathology. |
| Animal Model: | Male CD-1 mouse, male SD rat and male cynomolgus macaque[1] |
| Dosage: | 1-10 mg/kg |
| Administration: | PO or IV (Pharmacokinetic Analysis) |
| Result: | Showed promising human pharmacokinetics profile. |
