Table 3.
Single-dose PK parameters for GS-441524 in mice. Calculation of PK parameters for GS441524 following oral (50 mg/Kg) and intravenous (25 mg/Kg) administration of the ester prodrugs (5a, 5b, 5c and 5g·HBr) in CD-1 mice (N = 3 per group).
| Compd. (Route) | T1/2 | Tmax | Cmax | AUC_last | CL_obs | MRTINF_obs | Vss_obs | F |
|---|---|---|---|---|---|---|---|---|
| (h) | (h) | (ng/mL) | (h*ng/mL) | (mL/min/kg) | (h) | (L/kg) | (%) | |
| 5a (p.o.) | 1.11 | 0.33 | 7879 | 14,565 | – | 1.82 | – | 71.6 |
| 5a (i.v.) | 0.83 | – | – | 10,174 | 40.9 ± 9.1 | 1.07 | 2.59 | |
| 5b (p.o.) | 1.72 | 0.83 | 1506 | 2984 | – | 2.76 | 27.5 | |
| 5b (i.v.) | 0.61 | – | – | 5420 | 82.0 ± 24.3 | 0.78 | 3.86 | |
| 5c (p.o.) | 2.46 | 0.42 | 6677 | 13,817 | – | 2.16 | 86.6 | |
| 5c (i.v.) | 4.77 | – | – | 7981 | 52.5 ± 6.13 | 1.33 | 4.17 | |
| 5g·HBr (p.o.) | 2.71 | 0.25 | 3613 | 7112 | – | 3.00 | – | 98.7 |
| 5g·HBr (i.v.) | 2.48 | – | – | 3603 | 118 ± 128 | 2.23 | 15.6 |