Amenamevir

Amenamevir is a helicase-primase inhibitor which has potent antiviral activity against HSVs with an EC₅₀ of 14 ng/mL. IC50 & Target: EC50: 14 ng/mL (HSV)^[1] In Vitro: Amenamevir (ASP2151) inhibits the replication of the HSV strains isolated in Japan and the United States as well as the laboratory-stocked strains. The mean EC₅₀s of Amenamevir against HSV-1 and HSV-2 are 14 (range, 7.7 to 20) and 30 ng/mL (range, 15 to 58), respectively, whereas those of acyclovir (ACV) are 29 (range, 18 to 38) and 71 ng/mL (range, 45 to 95), respectively. The EC₅₀s of Amenamevir against HSV strains are significantly lower than those of ACV^[1]. In Vivo: Amenamevir (ASP2151) administration accelerates the reduction in virus titer in a dose-dependent manner in the range of 3 to 30 mg/kg/day. Amenamevir treatment decreases both lesion scores and HSV-1 titers in a dose-dependent manner, irrespective of the dosing interval. Based on the correlation curves, the PK parameters at which HSV-1 growth is completely suppressed by oral administration of Amenamevir are estimated to be 10,000 ng/mL or higher for the maximum concentration of drug in serum (C_max), 60 μg ? h/ml or higher for concentration-time curve over 24 h (AUC_24h), and 21 to 24 h for T_>100 . The mean concentration of Amenamevir in plasma at 5 days postinfection increases in a dose-dependent manner, with doses of 3 mg Amenamevir/g or higher significantly reducing the intradermal HSV-1 titer^[1].