Pharmacokinetic parameters of saquinavir in New Zealand White female rabbits after USI administration at 5 mg/kg in the absence or presence of CYP3A or P-gp inhibitors Pharmacokinetic parameters were analyzed based on systemic arterial concentrations of saquinavir. Data presented are mean and S.E.M. from 2 to 5 animals per treatment.
SQV | SQV + GF | SQV + MDZ | SQV + CsA | |
|---|---|---|---|---|
| Tmax (min) | 7.00 ± 1.22 | 17.5 ± 2.5* | 8.33 ± 1.67 | 96.7 ± 86.7 |
| Cmax (ng/ml) | 91.8 ± 30.2 | 93.8 ± 28.7 | 58.6 ± 23.4 | 242 ± 73 |
| ka** (min) | 0.164 ± 0.028 | 0.0876 ± 0.0192 | 0.365 ± 0.100 | 0.0855 ± 0.0300 |
| AUC0-t (ng·h/ml) | 64.1 ± 16.9 | 76.6 ± 20.2 | 123 ± 84 | 673 ± 476 |
| AUC0-∞ (ng·h/ml) | 72.7 ± 18.4 | 132 ± 15 | 406 ± 359 | 5140 ± 4860 |
| t1/2 (h) | 2.22 ± 0.34 | 10.7 ± 1.7* | 5.66 ± 3.40 | 15.4 ± 11.1 |
| CL/F (l/h/kg) | 88.9 ± 20.6 | 38.4 ± 4.4 | 103 ± 69 | 18.9 ± 13.6* |
| Vz/F (l/kg) | 269 ± 70 | 606 ± 164 | 307 ± 134 | 97.6 ± 47.1 |
| E H | 0.445 ± 0.130 | 0.404 ± 0.048 | 0.326 ± 0.165 | 0.187 ± 0.156 |
| CLH (l/h/kg) | 0.948 ± 0.382 | 1.08 ± 0.13 | 0.869 ± 0.438 | 0.499 ± 0.415 |
| F oral | 0.0408a | |||
| Fr | 1.00 | 1.82 ± 0.21 | 5.58 ± 4.95 | 10.9 ± 6.3 |