Assessment of the Mechanism for Remdesivir-Associated Clinical ALT Elevations Using DILIsym Quantitative Systems Toxicology Modeling

Authors: Yang K, Howell BA, Feng J, Babusis D, Cihlar T, Siler SQ
Conference: AASLD
Keywords: ALT, ALT elevation frequencies, celebrate qsp, COVID-19, DILIsym, mechanism
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Introduction

  • Remdesivir, a monophosphoramidate prodrug of a nucleoside analog, has been granted Emergency Use Authorization in the U.S. for the treatment of hospitalized COVID-19 patients.
  • In a Ph1 clinical study in healthy volunteers treated with the 150 mg daily dose of remdesivir for 7 or 14 days (higher than the current clinical dose) [1], reversible low- grade elevations of serum ALT and AST were observed at 5-25 days after the first dose in 8 out of 16 individuals.

By Kyunghee Yang, Brett A Howell, Joy Y. Feng, Darius Babusis, Tomas Cihlar, Scott Q Siler

(AASLD) The Liver Meeting, Nov. 13-16, 2020