Abstract
We developed unique small-molecule inhibitors of hepatitis C virus (HCV), which had
potent activity for HCV entry inhibition and multi-genotypic antiviral activity. In
this study, a sensitive and reliable method for the quantitation of JW5624 in rat
plasma was developed and validated using high performance liquid chromatography. Chromatographic
separation was achieved using a reversed-phase (C18) column. The mobile phase, 0.02 M
ammonium acetate buffer:acetonitrile (30:70, v/v), was run at a flow rate of 1.0 mL/min,
and the column eluent was monitored using an ultraviolet detector at 254 nm at room
temperature. The retention times of sildenafil (an internal standard), and JW5624
were approximately 5.9 and 7.3 min, respectively. The detection limit of JW5624 in
rat plasma was 0.03 μg/mL. Pharmacokinetic parameters of JW5624 was evaluated after
intravenous (i. v.; at doses of 5 mg/kg) and oral (p.o.; at doses of 10 mg/kg) administration
of JW5624 in rats. After p.o. administration (10 mg/kg) of JW5624, F value was approximately 71.0%. These results suggest that JW5624 can be a potential
candidate drug for the development of HCV entry inhibitors.
Key words JW5624 - Hepatitis C virus - bioavailability - pharmacokinetics - rats
