Pharmacokinetic parameters of E2074 in rats, dogs, and monkeys
The pharmacokinetic parameters represent the mean ± S.E. of three animals or five rats, or the mean of two monkeys.
| Rat | Dog | Monkey | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| i.v. | Oral | Oral | Oral | i.v. | Oral | Oral | i.v. | Oral | Oral | |
| Dose (mg/kg) | 1 | 3 | 10 | 30 | 1 | 3 | 10 | 1 | 3 | 10 |
| tmax (h) | NA | 0.25–0.5a | 0.25 | 0.25–0.5 | NA | 0.5–1.0 | 0.5–1.0 | NA | 2b | 1–2 |
| Cmax (µg/ml) | NA | 0.02 ± 0.01a | 0.20 ± 0.03 | 1.36 ± 0.49 | NA | 0.02 ± 0.01 | 1.07 ± 0.27 | NA | 0.04b | 0.47 ± 0.06 |
| t1/2 (h) | 0.85 ± 0.02 | 0.50 ± 0.02a | 0.57 ± 0.03 | 1.36 ± 0.33 | 1.04 ± 0.02 | 0.91 ± 0.16 | 1.82 ± 0.35 | 3.18 ± 0.92 | 5.42b | 2.95 ± 0.60 |
| AUC (µg·h/ml) | 0.31 ± 0.01 | 0.02 ± 0.01a | 0.17 ± 0.02 | 1.42 ± 0.46 | 0.62 ± 0.11 | 0.02 ± 0.01 | 2.73 ± 1.23 | 0.76 ± 0.09 | 0.18b | 1.58 ± 0.15 |
| CL (l/h/kg) | 3.21 ± 0.12 | NA | NA | NA | 1.70 ± 0.26 | NA | NA | 1.35 ± 0.14 | NA | NA |
| Vss (l/kg) | 2.54 ± 0.08 | NA | NA | NA | 1.84 ± 0.32 | NA | NA | 3.98 ± 0.30 | NA | NA |
| BA (%) | NA | 2.6 | 5.3 | 15.1 | NA | 1.2 | 43.7 | NA | 7.8 | 20.9 |
AUC, area under the plasma concentration curve; BA, bioavailability; CL, clearance; E2074, 2-[(2R)-2-fluoro-3-{(3r)-[(3-fluorobenzyl)oxy]-8-azabicyclo[3.2.1]oct-8-yl}propyl]-4,5-dimethyl-2,4-dihydro-3H-1,2,4-triazol-3-one; NA, not applicable; t1/2, half-life; tmax, time to reach Cmax; Vss, steady-state volume of distribution.
↵a Mean ± S.E. of three animals or five rats.
↵b Mean of two monkeys.