Table 2. Pharmacokinetic parameters of SC81458 and SC83288.
| Compound |
SC81458 |
SC83288 |
||||||
|---|---|---|---|---|---|---|---|---|
| Application |
i.p. |
i.v. |
||||||
| Species | Mouse | Mouse | Rat | Dog | Cynomolgus | |||
| Dose (mg kg−1) | 20 | 2.5 | 5 | 10 | 2 | 2 | 1.7 | 2 |
| AUC0-inf (ng h ml−1) | 4,342 | 646 | 1,089 | 2,019 | 891 | 1,419 | 2,262 | 4,253 |
| C0 (ng ml−1) | 0 | 0 | 0 | 0 | 3,644 | 4,375 | 5,579 | 7,338 |
| Cmax (ng ml−1) | 7,384 | 610 | 1,338 | 1,711 | 2,560 | 3,283 | 4,564 | 6,569 |
| tmax (min) | 30 | 5 | 5 | 30 | 5 | 5 | 5 | 5 |
| t1/2 initial (min) | NC | NC | NC | NC | 9 | 9 | 12 | 16 |
| t1/2 terminal (min) | 860 | 100 | 73 | 46 | 43 | 625 | 90 | 320 |
| t1/2 effective (min) | 52 | 33 | 29 | 55 | 12 | 52 | 35 | 62 |
| MRT0-t (h) | 1.24 | 0.79 | 0.69 | 1.33 | 0.28 | 1.25 | 0.84 | 1.50 |
| CL (ml h−1 kg−1) | 4,607 | 3,870 | 4,590 | 4,953 | 2245 | 1,410 | 884 | 470 |
| VC (ml kg−1) | NC | NC | NC | NC | 549 | 457 | 359 | 273 |
| F (%) | 62 | 58 | 49 | 45 | 100 | 100 | 100 | 100 |
AUC, area under the concentration-time curve; C0, initial drug plasma concentration; Cmax, observed maximum plasma concentration after administration; CL, total plasma clearance of drug after administration; F, relative bioavailability compared to i.v.; MRT, mean residence time of the unchanged drug in the systemic circulation; NC, not calculated; tmax, time of Cmax; t1/2, time required for the concentration to fall to 50% of its initial value; Vc, apparent volume of the central or plasma compartment.
Data were examined using a non-compartment analysis.