MK-0608 is an orally bioavailable HCV replication inhibitor in vitro(EC50 = 0.3 μM and EC90=1.3 μM in the subgenomic-replicon assay).

MK-0608 inhibit viral RNA replication in the subgenomic HCV genotype 1b replicon, with a 50% effective concentration (EC(50)) of 0.3 microM (EC(90) = 1.3 microM). A?robust antiviral effect on the administration of MK-0608 to HCV-infected chimpanzees.

MK-0608 was administered to HCV-infected chimpanzees, resulting in dose- and time-dependent decreases in plasma viral loads.?In separate experiments, chimpanzees dosed for 7 days with MK-0608 at 0.2 and 2 mg per kg of body weight per day by intravenous administration experienced average reductions in viral load of 1.0 and >5 log(10) IU/ml, respectively.?Two other HCV-infected chimpanzees received daily doses of 1 mg MK-0608 per kg via oral administration.?After 37 days of oral dosing, one chimpanzee with a high starting viral load experienced a reduction in viral load of 4.6 log(10), and the viral load in the other chimpanzee fell below the limit of quantification (LOQ) of the HCV TaqMan assay (20 IU/ml).?Importantly, viral load remained below the LOQ throughout the duration of dosing and for at least 12 days after dosing ended.