TABLE 1.
Values of pharmacokinetic parameters for neuraminidase inhibitors administered as 10 mg-eq/kg doses to ratsa
| Compound | Route | AUC0–24 (mg · h/liter) | Cmax (μg/ml) | tmax (h) | CL (liters/h/kg) | t1/2 (h)b | VSS (liters/kg) | F as parent compound (%) |
|---|---|---|---|---|---|---|---|---|
| GS 4071 | i.v. | 8.4 ± 1.4 | 1.5 ± 0.3 | 1.6 ± 0.4 | 1.3 ± 0.6 | 100 | ||
| Oral | 0.3 ± 0.1 | 0.03 ± 0.00 | 4.0 ± 1.6 | 10.6 ± 5.5 | 4.3 ± 1.6 | |||
| GS 4104 | i.v. | 6.6 ± 1.2 | 1.8 ± 0.3 | 6.2 ± 2.3 | 3.1 ± 0.9 | 79 ± 14 | ||
| Oral | 3.0 ± 0.9 | 0.47 ± 0.13 | 1.6 ± 1.6 | 7.0 ± 0.6 | 35 ± 11 | |||
| GS 4116 | i.v. | 9.0 ± 1.7 | 1.3 ± 0.2 | 5.7 ± 0.8 | 1.1 ± 0.3 | 100 | ||
| Oral | 0.4 ± 0.1 | 0.06 ± 0.01 | 1.9 ± 1.5 | 20.1 ± 7.0 | 4.0 ± 1.0 | |||
| GS 4109 | i.v. | 9.2 ± 0.9 | 1.2 ± 0.1 | 6.0 ± 1.0 | 1.6 ± 0.3 | 102 ± 10 | ||
| Oral | 0.2 ± 0.1 | 0.03 ± 0.00 | 0.8 ± 0.8 | 18.0 ± 5.3 | 2.1 ± 1.1 | |||
| Zanamivir (GG167) | i.v. | 5.5 ± 1.5 | 1.9 ± 0.6 | 1.1 ± 0.3 | 0.8 ± 0.1 | 100 | ||
| Oral | 0.2 ± 0.2 | 0.06 ± 0.01 | 1.2 ± 0.7 | 1.8 ± 0.6 | 3.7 ± 2.3 |
a
Values are means ± standard deviations for four animals on the basis of the levels of parent compound in plasma.
b
The terminal t1/2 was estimated on the basis of the values at 6 and 12 h for the samples from animals given drug i.v. and the values at 12 and 24 h for the samples from animals given drug orally (or values obtained at 4 and 12 h for orally administered zanamivir).