Animal experiment:

Mice[1]For the first animal experiment, Inarigivir is prepared fresh daily at a dosage of 100 mg/kg of body weight /day, which is equal to 170 mol/kg/day, and is injected intraperitoneally (i.p.) using cremaphor-ethanol-saline (CES) (10:10:80) or physiological saline as vehicles. ADV, the positive control, is prepared using the CES vehicle. A dosage of 10 mg/kg/day (19.9 mol/kg/day) is used. In the second experiment to determine the minimal effective concentration, Inarigivir is prepared in sterile saline in onehalf-log dilutions from 50 to 0.05 mg/kg/day. The drug is delivered i.p. in a volume of 0.1 ml. Liver samples are analyzed for HBV DNA, HBV RNA, and HBcAg, and serum samples are processed for HBV DNA, HBeAg, and HBsAg[1].

Inarigivir (ORI-9020;SB-9000) is a dinucleotide which can significantly reduce liver HBV DNA in transgenic mice expressing hepatitis B virus.

I.p. injection of Inarigivir at 100 mg/kg/day significantly reduces viral DNA in the liver and shows anti-HBV activity similar ADV positive control. Serum HBV DNA is not reduced in response to treatment. Inarigivir does not affect levels of HBV RNA in liver, levels of HBeAg in serum, or mean titers of HBsAg. The minimal effective dose is identified to be between 1.6 and 0.5 mg/kg/day using liver HBV DNA values[1].

[1]. Iyer RP, et al. Anti-hepatitis B virus activity of ORI-9020, a novel phosphorothioate dinucleotide, in a transgenic mouse model. Antimicrob Agents Chemother. 2004 Jun;48(6):2318-20.