TABLE 10.
ABI-H0731 pharmacokinetics in mouse, rat, dog, and monkey after single-dose i.v. or oral solution administrationa
| Speciesb | Routec | Dose (mg/kg) | Cmax (ng/ml) | Tmax (h) | AUCinf (ng · h/ml) | CL (ml/min/kg) | Vss (liters/kg) | T1/2 (h) | %F |
|---|---|---|---|---|---|---|---|---|---|
| Mouse | i.v. | 1 | 2,070 | 8.05 | 2.16 | 3.55 | 84 | ||
| p.o. | 5 | 1,420 | 1.00 | 8,690 | 3.03 | ||||
| Rat | i.v. | 1 | 1,670 | 10.1 | 3.47 | 4.92 | 95 | ||
| p.o. | 2 | 324 | 1.00 | 3,160 | 6.13 | ||||
| Dog | i.v. | 2 | 2,890 | 14.7 | 1.56 | 2.46 | 49 | ||
| p.o. | 3 | 861 | 0.667 | 2,150 | 3.34 | ||||
| Monkey | i.v. | 0.5 | 1,750 | 4.86 | 4.06 | 12.6 | 55 | ||
| p.o. | 2 | 353 | 3.33 | 4,340 | 11.6 | ||||
a
Cmax, maximum concentration of drug in serum; AUCinf, area under the concentration-time curve from time zero to infinity; Vss, volume of distribution at steady state.
b
For mice, a composite study design was utilized (n = 3/time point/dose group). In other species, individual animals were sampled serially (n = 3/dose group).
c
For intravenous (i.v.) and oral (p.o.) administration, ABI-H0731 was formulated in a solution containing 5% (vol/vol) NMP–5% (vol/vol) Solutol HS-15–90% (vol/vol) normal saline.