TABLE 1.
Repeat-dose oral toxicity studies with telbivudine in mice, rats, and monkeys
| Study type and duration | Species | Doses (mg/kg/day) | Animal assignment |
|---|---|---|---|
| 4-wk toxicity with toxicokinetics | Mouse (CB6F1/Crl: BR) | 0, 500, 1,000, 2,000 | 10/sex/group |
| 13-wk toxicity with toxicokinetics | Mouse [Crl:CD-1(ICR) BR] | 0, 500, 1,000, 3,000 | 10/sex/group |
| 28-day toxicity with toxicokinetics | Rat [Crl:CD(SD) BR] | 0, 500, 1,000, 2,000 | 10/sex/group |
| 6-mo toxicity with 3-mo interim sacrifice | Rat [Crl:CD(SD) BR] | 0, 250, 500, 1,000 | 10/sex/groupa |
| 28-day toxicity with toxicokinetics | Monkey (cynomolgus) | 0, 500, 1,000, 2,000 | 10/sex/group |
| 9-mo toxicity with 3-mo interim sacrifice | Monkey (cynomolgus) | 0, 250, 500, 1,000 | 3-4/sex/groupb |
a
An additional 5 rats/sex were assigned to control and high-dose groups to serve as a 1-month recovery subgroup.
b
Three monkeys/sex/group were scheduled to be sacrificed following 3 months of dosing and 4 monkeys/sex/group were sacrificed following 9 months of dosing. An additional 2 monkeys/sex were assigned to control and high-dose groups to serve as a 2-month recovery subgroup.