Pharmacokinetic evaluation of A-131701 after single i.v. or p.o. dosing in rat, dog or monkey
| Species | Dose | Dose Route | t1/2 | Vβ | CLp | AUC0–∞ | Cmax | Tmax | F | n |
|---|---|---|---|---|---|---|---|---|---|---|
| mg/kg | hr* | l/kg | l/hr/kg | μg · hr/ml | μg/ml | hr | % | |||
| Rat | 5 | i.v. | nf | nc | 0.16 (0.00) | 31.4 (0.40) | 4 | |||
| 1 | p.o. | 2.4 | 1.62 (0.58) | 0.84 (0.44) | 0.5 (0.4) | 25.7 (9.3) | 3 | |||
| 5 | p.o. | 4.8 | 12.0 (4.43) | 5.89 (3.36) | 0.25 (0.0) | 38.1 (14.1) | 3 | |||
| 10 | p.o. | 3.9 | 17.4 (2.66) | 7.82 (2.61) | 0.25 (0.0) | 27.6 (4.2) | 3 | |||
| Dog | 0.5 | i.v. | 0.42 | 0.50 | 0.96 (0.34) | 0.56 (0.18) | 3 | |||
| 1 | i.v. | 0.46 | 0.53 | 0.74 (0.08) | 1.36 (0.15) | 3 | ||||
| 2.5 | i.v. | 0.64 | 0.52 | 0.51 (0.02) | 4.65 (0.46) | 3 | ||||
| 0.5 | p.o. | 0.41 | 0.16 (0.08) | 0.21 (0.11) | 0.3 (0.1) | 29.3 (13.7) | 3 | |||
| 1 | p.o. | 0.57 | 0.75 (0.29) | 0.77 (0.31) | 0.4 (0.1) | 55.2 (21.7) | 3 | |||
| 2.5 | p.o. | 0.83 | 4.89 (1.20) | 4.12 (1.27) | 0.3 (0.0) | 52.6 (12.9) | 3 | |||
| Monkey | 2.5 | i.v. | 2.0 | 0.18 | 0.05 (0.01) | 53.8 (8.28) | 3 | |||
| 0.5 | p.o. | 1.2 | 2.46 (1.40) | 0.86 (0.29) | 0.8 (0.6) | 22.8 (13.0) | 3 | |||
| 1 | p.o. | 1.4 | 5.06 (0.51) | 1.14 (0.07) | 1.2 (0.8) | 23.5 (2.4) | 3 | |||
| 5 | p.o. | 1.3 | 40.6 (20.8) | 15.8 (11.2) | 32.0 (2.8) | 37.8 (19.4) | 3 |
Rats, dogs and monkeys were administered A-131701 at various doses either via the i.v. or p.o. route as described under “Methods.” At periodic sampling intervals thereafter, blood samples were drawn, plasma isolated and the concentration of A-131701 determined by high-performance liquid chromatography, as described under “Methods.” Data are expressed as means (standard deviation). * Harmonic mean; nf, unable to calculate plasma elimination half-life; nc, unable to calculate.