Table 1.
Pharmacokinetic parameters of R-125224 after intravenous administration to cynomolgus monkeys at single doses of 0.4, 1.2, 6 and 30 mg·kg−1
| Dose (mg·kg−1) | AUC0–28 daya(µg·day·mL−1) | AUC0–28 day predictedb(µg·day·mL−1) | AUC0–7 dayb(µg·day·mL−1) | MRTlasta (day) | t1/2b (day) | CLtotalb(mL·day−1·kg−1) | Vssb(mL·kg−1) |
|---|---|---|---|---|---|---|---|
| 0.4 | 18.7 ± 8.8 | 14.5 ± 4.4 | 13.1 ± 4.3 | 5.33 ± 3.46 | 2.78 ± 1.20 | 27.9 ± 7.6 | 94.9 ± 65.8 |
| 1.2 | 54.5 ± 14.9 | 58.4 ± 18.5 | 48.9 ± 9.4 | 2.61 ± 0.89 | 2.60 ± 1.14 | 22.0 ± 6.9 | 67.2 ± 10.3 |
| 6 | 558 ± 69 | 676 ± 90* | 391 ± 48 | 4.75 ± 0.51 | 6.34 ± 0.93 | 8.40 ± 1.39 | 74.7 ± 10.3 |
| 30 | 4420 ± 1860 | 4670 ± 1370 | 2480 ± 550 | 6.53 ± 2.07 | 7.38 ± 1.40 | 6.21 ± 1.79 | 62.9 ± 9.0 |
a
Parameters were calculated using the plasma concentrations at days 0–28.
b
Parameters were calculated using the plasma concentrations at days 0–7.
Statistical analysis comparing AUC0–28 day predicted to AUC0–28 day were performed with paired t-test;
*
P < 0.05.