TABLE 6.
Steady-state exposure to telbivudine at the NOAEL and animal-to-human exposure multiples in mice, rats, rabbits, and monkeys
| Study description | NOAEL (mg/kg/day) | Cmaxa [μg/ml (multiple)]b | AUC0-24a [μg·h/ml (multiple)]b |
|---|---|---|---|
| 13-wk toxicity in mice with toxicokinetics | 3,000 | 141 (41) | 595 (22) |
| 6-mo toxicity in rats with 3-mo interim sacrifice | 1,000 | 35.8 (11) | 169 (6) |
| 9-mo toxicity in monkeys with 3-mo interim sacrifice | 500 | 21.1 (6) | 126 (5) |
| Fertility, early embryonic development, and embryo-fetal development in male and female rats (segments I and II) | 1,000 | 35.8 (11) | 169 (6) |
| Fertility in male rats (segment I) | 2,000 | 50.5 (15) | 398 (14) |
| Fertility in female rats (segment I) | 2,000 | 50.5 (15) | 398 (14) |
| Embryo-fetal development in rabbits (segment II) | 1,000 | 66.4 (20) | 1,023 (37) |
| Multiple generation development study in rats (segment III) | 1,000 | 35.8 (11) | 169 (6) |
a
Animal steady-state Cmax and AUC0-24 values were the averages of mean male and female data.
b
Human steady-state Cmax (3.4 μg/ml) and AUC0-24 (27.5 μg·h/ml) values were obtained from healthy subjects following 7 days of once daily oral administration of 600 mg of telbivudine (31), the approved therapeutic dose for patients with chronic HBV infection.