JNJ-632 is a capsid assembly modulator inhibiting hepatitis B virus (HBV). JNJ-632 inhibits HBV DNA HepG2.2.15 and HBV DNA HepG2.117 with EC50s of 0.12 and 0.43 μM, respectively. In the high-content multiparameter cytotoxicity (HepG2), JNJ-632 shows EC20s in the 10-30 μM range (considered weakly cytotoxic).
The single dose PK profile of JNJ-632 is evaluated in C57BL/6 mice following intravenous (iv) and oral (po) administration. JNJ-632 has a moderate plasma clearance of 34 mL/min/kg and a moderate volume of distribution of 1.3 L/kg. The oral bioavailability is 40% following oral administration of 10 mg/kg and 66% following oral administration of 50 mg/kg. JNJ-632 has moderate terminal elimination half-life with t1/2s of 0.42±0.06 h, 1.1±0.67 h, 2.4±2.3 h, and 5.3±0.1 h for 2.5 mg/kg (iv), 10 mg/kg (po), 50 mg/kg (po), and 50 mg/kg (sc).To circumvent the first pass metabolism, JNJ-632 is also dosed subcutaneously at 50 mg/kg in C57BL/6 mice and this results in a concentration in plasma after 24 h of dosing of 102 ng/mL and concentration in liver after 24 h of dosing of 1297 ng/g.
The pharmacokinetic profile is evaluated in fed male C57BL/6 mice (n=3/group). Mice are i.v. injected with JNJ-632 at 2.5 mg/kg,
formulated as a 0.5 mg/mL solution in PEG400/water (70/30), and blood
samples are collected from the saphenous vein at 0.05, 0.17, 0.5, 1, 2,
4, 7, and 24 hours into EDTA-containing microcentrifuge tubes. JNJ-632 is administered p.o. at 10 and 50 mg/kg,
formulated as 0.5 and 2.5 mg/mL suspension in methocel 0.5% w/v, and
blood samples are collected from the saphenous vein at 0.5, 1, 2, 4, 7, 9
and 24 hours into EDTA-containing microcentrifuge tubes. JNJ-632 is administered s.c. at 50 mg/kg, and blood samples are collected. The blood samples are immediately centrifuged at 4°C and the plasma was stored at -20°C.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.