Table 4.
Pharmacokinetic parameters for SR13668a
| iv, 1 mg/kg (6 mg/m2) |
po, 1 mg/kg (6 mg/m2) |
po, 10 mg/kg (60 mg/m2) |
po, 30 mg/kg (180 mg/m2) |
|||||
|---|---|---|---|---|---|---|---|---|
| Male | Female | Male | Female | Maleb | Female | Male | Female | |
| t1/2 (h) | 4.4 ± 0.4 | 5.6 ± 2.2 | 7.5 ± 1.3 | 7.1 ± 0.6 | 5.6 | 9.0 ± 4.4 | 9.6 ± 1.3 | 7.3 ± 1.1 |
| Tmax (h) | NA | NA | 4.0 ± 4.4 | 3.3 ± 1.2 | 5.7 ± 3.4 | 5.3 ± 1.2 | 6.3 ± 2.5 | 8.0 ± 1.7 |
| C0 (ng/ml) | 1,435.7 ± 233.2 | 1,557.8 ± 299.4 | NA | NA | NA | NA | NA | NA |
| Cp (ng/ml) | 925.8 ± 82.4 | 933.0 ± 113.4 | 17.1 ± 10.9 | 23.2 ± 18.4 | 130.1 ± 63.6c | 531.5 ± 216.8c | 455.5 ± 85.5c | 883.9 ± 82.4c |
| AUClast (ng h/ml) | 1,124.7 ± 99.2c | 1,601.0 ± 157.1c | 130.3 ± 26.2 | 236.6 ± 118.0 | 1,446.6 ± 277.6c | 6,560.6 ± 2,133.3c | 7,038.1 ± 1,347.3c | 12,365.0 ± 1,957.0c |
| AUCinf (ng h/ml) | 1,138.7 ± 100.5c | 1,668.8 ± 114.8 | 143.7 ± 22.6 | 262.37 ± 127.1 | 1,699.2 | 8,236 ± 2,797.3c | 8,676.9 ± 1,300.1c | 13,857.9 ± 1,961.5c |
| V or V/F (L/kg) | 5.6 ± 0.8 | 4.8 ± 2.0 | 77.7 ± 26.1 | 49.7 ± 32.4 | 49.4c | 16.9 ± 5.2c | 49.3 ± 12.4c | 23.2 ± 6.3c |
| Cl or Cl/F (ml/h/kg) |
883 ± 82c | 601 ± 41c | 7,085.3 ± 1,196.9 | 4,767.0 ± 3,002.3 | 5924c | 1,340.3 ± 559.7c | 3,507.0 ± 495.3c | 2,193.0 ± 295.3c |
| MRT (h) | 3.6 ± 0.3 | 5.8 ± 2.0 | 10.4 ± 2.2 | 10.6 ± 1.2 | 9.1 | 14.8 ± 7.0 | 14.9 ± 1.5 | 11.8 ± 0.8 |
| F (%) | 12.6 ± 2.0 | 15.7 ± 7.6 | 14.9 | 49.4 ± 16.8 | 25.4 ± 3.8 | 27.7 ± 3.9 | ||
Values represent the mean ± SD of n = 3 unless noted otherwise
a
Parameters requiring calculation of the terminal phase are for n = 2 rats, other parameters calculated with n = 3
b
Values of males and females signiWcantly diVerent, P < 0.05