TABLE 7.
DMPK parameters and in vivo efficacy of GSK9574
| Dose group | Mean log VL reductiona |
Mean C12 (ng/ml)b |
Compound liver/plasma ratio | PA EC90 (ng/ml)c | Mean liver concn/PA EC90 ratio | ||
|---|---|---|---|---|---|---|---|
| At nadir | At day 7 | Plasma | Liver | ||||
| 10 mg/kg GSK9574 BID | 3.7 | 2.5 | 123 | 908 | 7.4 | 16.9 | 53.8 |
| 30 mg/kg GSK9574 BID | 3.6 | 3.4 | 380 | 2,995 | 7.9 | 16.9 | 177.2 |
| 100 mg/kg GSK9574 BID | 3.3 | 3.3 | 2,853 | 11,451 | 4.0 | 16.9 | 677.6 |
| 100 mg/kg HCV-796 BID | 2.2 | 1.5 | 127 | 3,493 | 27.4 | 14.5 | 240.9 |
| 10 mg/kg BILN-2061 BID | 2.1 | 1.8 | 3 | 86 | 25.0 | 85.5 | 1.0 |
a
Viral load (VL) reduction data were calculated from the serum samples relative to those taken on day −2.
b
Plasma and liver compound concentrations were quantitated from samples taken 12 h after the final dose (C12).
c
Protein-adjusted (PA) EC90 data were calculated from replicon EC50 determinations as modified by the 5.8-fold serum shift determined with the 40% human serum replicon assay.