TABLE 4.
Pharmacokinetics of ABT-378 administered in combination with ritonavira
| Species | Dose (mg/kg)
|
Ritonavir
|
ABT-378
|
n | Cmax/EC50b | Ct/EC50b | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| ABT-378 | RTV | Cmax (μg/ml) | Tmax (h) | AUC0–t (μg · h/ml) | Cmax (μg/ml) | Tmax (h) | AUC0–t (μg · h/ml) | ||||
| Rat | 10 | 0 | 0.96 | 0.8 | 1.92 | 4 | 15.0 | ||||
| 10 | 10 | 1.13 | 2.5 | 4.83 | 3.68 | 7.3 | 23.41 | 3 | 57.5 | 55.1 | |
| 10 | 5 | 0.15 | 0.6 | 0.38 | 2.11 | 4.5 | 12.29 | 4 | 33.0 | 20.5 | |
| 10 | 1 | 0.00 | 0.00 | 1.19 | 1.0 | 4.37 | 3 | 18.6 | 2.1 | ||
| 5 | 5 | 0.12 | 0.8 | 0.22 | 1.55 | 6.0 | 9.28 | 4 | 24.2 | 24.0 | |
| 5 | 2.5 | 0.00 | 0.00 | 1.14 | 4.1 | 5.26 | 4 | 17.8 | 7.4 | ||
| 5 | 1 | 0.00 | 0.00 | 1.31 | 1.2 | 5.72 | 4 | 20.5 | 6.1 | ||
| 3 | 3 | 0.06 | 0.8 | 0.03 | 0.91 | 5.0 | 4.20 | 4 | 14.2 | 5.4 | |
| 2.5 | 5 | 0.13 | 2.8 | 0.41 | 1.67 | 6.0 | 10.32 | 4 | 26.1 | 22.6 | |
| Monkey | 10 | 0 | 0.00 | 0.00 | 3 | ||||||
| 10 | 10 | 1.48 | 3.3 | 5.01 | 3.06 | 3.3 | 14.72 | 3 | 47.8 | 4.2 | |
| Dog | 5 | 0 | 0.00 | 0.00 | 3 | ||||||
| 5 | 5 | 1.32 | 0.8 | 2.19 | 2.50 | 1.3 | 11.26 | 3 | 39.1 | 0.70 | |
a
Data are provided as mean values. AUC0–t, area under the concentration-time curve from time zero to time t; Ct, concentration in plasma derived from the last sampling time point in each pharmacokinetic study (8 h for rats and 12 h for monkeys and dogs); RTV, ritonavir.
b
EC50 for anti-HIV-1IIIB activity in MT4 cells in the presence of 50% HS plus 10% fetal calf serum; the EC50 of ABT-378 was 0.064 μg/ml.