TABLE 3.
In vivo pharmacokinetic parameters for UCT943 across mouse, rat, dog, and monkey species calculated from noncompartmental analysis
| Parameterb | Value for the parameter by species and route of drug administration (SD) |
|||||||
|---|---|---|---|---|---|---|---|---|
| Mouse |
Rat |
Dog |
Monkey |
|||||
| i.v. | p.o. | i.v. | p.o. | i.v. | p.o. | i.v. | p.o. | |
| Dose (mg/kg) | 5 | 20 | 5 | 20 | 2 | 10 | 2 | 10 |
| t1/2 (h) | 6.4 (0.7) | 5.7 (0) | 7.4 (0.6) | 5.3 (0.3) | 13.0 | 16.1 | 28.6 | 34.6 |
| Plasma Vss (liters/kg) | 13.1 (1.1)a | 11.5 (2.1)a | 7.1 (0.9) | 8.7 (1.0) | ||||
| CLb (ml/min/kg) | 12.6 (2.4) | 9.5 (1.6) | 3.3 (0.6)a | 2.0 (0.3)a | ||||
| CLp (ml/min/kg) | 24.0 (4.6)a | 20.0 (3.4)a | 7.5 (1.2) | 3.9 (0.6) | ||||
| Plasma AUC0-∞ (min · μM) | 497 (8.5)a | 1,310 (202)a | 725 (109)a | 2,843 (480)a | 634 (89) | 2,335 (754) | 1,192 (164) | 4,745 (761) |
| Plasma Cmax (μM) | 1.2 (0.2)a | 1.7 (0.3)a | 2.4 (0.2)a | 2.1 (0.7)a | 1.0 (0.1) | 2.3 (0.4) | 1.5 (0.03) | 2.1 (0.4) |
| Tmax (h) | 4.0 (3.6) | 12.0 | 2.3 (1.5) | 7.0 (1.7) | ||||
| F (%) | 66 (10) | 98 (4.9) | 74 (23.7) | 80 (12.8) | ||||
a
Blood values were scaled to plasma values using B/P ratios of 1.9, 2.1, 2.3, and 2.0 for mice, rats, dogs, and monkeys, respectively.
b
CLb, blood clearance; CLp, plasma clearance; AUC0-∞, area under the concentration-time curve from 0 h to infinity; F, bioavailability.