Table 4.
Male | Female | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Dose (mg/kg) (q.d.) | Dose (mg/kg) (q.d.) | |||||||||||
Study phase | Tissue | Findings | 0 | 0a | 60 | 200 | 1,000 | 0 | 0a | 60 | 200 | 1,000 |
Dosing | Liver | Hypertrophy, hepatocyte; periportal | 0/10 | 0/10 | 0/10 | 0/10 | 6/10b | 0/10 | 0/10 | 0/10 | 3/10b | 10/10b |
Minimal (Grade 1) | 0/10 | 0/10 | 0/10 | 0/10 | 1/10b | 0/10 | 0/10 | 0/10 | 3/10# | 2/10# | ||
Mild (Grade 2) | 0/10 | 0/10 | 0/10 | 0/10 | 5/10b | 0/10 | 0/10 | 0/10 | 0/10 | 8/10b | ||
Vacuolation, hepatocyte; periportal | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 4/10 | 5/10 | 3/10 | 5/10 | 10/10 | ||
Minimal (Grade 1) | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 4/10 | 5/10 | 3/10 | 5/10 | 6/10 | ||
Mild (Grade 2) | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 4/10b | ||
Thyroid gland | Hypertrophy, follicular cell | 0/10 | 0/10 | 0/10 | 0/10 | 8/10b | 0/10 | 0/10 | 0/10 | 0/10 | 8/10b | |
Minimal (Grade 1) | 0/10 | 0/10 | 0/10 | 0/10 | 6/10b | 0/10 | 0/10 | 0/10 | 0/10 | 6/10b | ||
Mild (Grade 2) | 0/10 | 0/10 | 0/10 | 0/10 | 2/10b | 0/10 | 0/10 | 0/10 | 0/10 | 2/10b | ||
Pituitary gland | Vacuolation, endocrine cells, pars distalis | 0/10 | ND | ND | ND | 0/10 | 0/10 | ND | ND | ND | 0/10 | |
Minimal (Grade 1) | 0/10 | ND | ND | ND | 0/10 | 0/10 | ND | ND | ND | 0/10 | ||
Mild (Grade 2) | 0/10 | ND | ND | ND | 0/10 | 0/10 | ND | ND | ND | 0/10 | ||
Recovery | Liver | Hypertrophy, hepatocyte; periportal | 0/5 | 0/5 | ND | 0/5 | 0/5 | 0/5 | 0/5 | ND | 0/5 | 0/5 |
Minimal (Grade 1) | 0/5 | 0/5 | ND | 0/5 | 0/5 | 0/5 | 0/5 | ND | 0/5 | 0/5 | ||
Vacuolation, hepatocyte; periportal | 0/5 | 0/5 | ND | 0/5 | 0/5 | 4/5 | 2/5 | ND | 4/5 | 4/5 | ||
Minimal (Grade 1) | 0/5 | 0/5 | ND | 0/5 | 0/5 | 4/5 | 2/5 | ND | 4/5 | 4/5 | ||
Thyroid gland | Hypertrophy, follicular cell | 0/5 | 0/5 | ND | ND | 0/5 | 0/5 | 0/5 | ND | ND | 0/5 | |
Minimal (Grade 1) | 0/5 | 0/5 | ND | ND | 0/5 | 0/5 | 0/5 | ND | ND | 0/5 | ||
Pituitary gland | Vacuolation, endocrine cells, pars distalis | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND | |
Minimal (Grade 1) | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
aDenotes MTBE control.
bDenotes nirmatrelvir-related finding.
Values represent the number of animals with findings compared with the total number of animals per group. ND, not determined.