Pharmacokinetic and Pharmacodynamic Analysis of the 3CL Protease Inhibitor Ensitrelvir in a SARS-CoV-2 Infection Mouse Model.

ABSTRACT: The small-molecule antiviral drug ensitrelvir targets the 3C-like protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study evaluated its inhibitory effect on viral replication in a delayed-treatment mouse model and investigated the relationship between pharmacokinetic (PK) parameters and pharmacodynamic (PD) effects. SARS-CoV-2 gamma-strain-infected BALB/c mice were orally treated with various doses of ensitrelvir starting 24 h post-infection. Effectiveness was determined 48 h after first administration based on lung viral titers. Ensitrelvir PK parameters were estimated from previously reported plasma concentration data and PK/PD analyses were performed. Ensitrelvir doses ≥ 16 mg/kg once daily, ≥8 mg/kg twice daily, or ≥8 mg/kg thrice daily for two days signifi

SUBMITTER: Fukao K 

PROVIDER: S-EPMC10612060 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature