Population Pharmacokinetics Analysis for Molnupiravir in Adults with COVID-19

Authors: Gao W, Bihorel S, Humphrey RL, Cao Y, Chawla A, Birger R, Sardella S, Kondragunta S, Jayaraman B, Painter W, Holman W, Stone J
Conference: ACoP
Keywords: COVID-19, PK analysis, SARS-CoV-2
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

  • There is an urgent need for safe and effective oral treatments for COVID-19 that reduce progression to severe illness and risk of hospitalization or death
  • Molnupiravir (MOV, MK-4482, EIDD-2801) is an orally available, ribonucleoside prodrug of β-D-N4-hydroxycytidine (NHC), with sub-micromolar potency against SARS-CoV-21
  • NHC is phosphorylated intracellularly to NHC triphosphate, its pharmacologically active form, and following its incorporation into the viral genome by the viral RNA polymerase during viral replication, it acts by inducing viral error catastrophe resulting from accumulation of deleterious mutations to a threshold beyond which the virus cannot replicate2
  • NHC circulates in plasma and is the primary pharmacokinetics (PK) measure for the clinical program

By Wei Gao, Sebastien Bihorel, Rebecca Humphrey, Youfang Cao, Akshita Chawla, Ruthie Birger, Susanne Sardella, Sindhuri Kondragunta, Bhuvana Jayaraman, Wendy Painter, George Painter, Wayne Holman, Julie Stone

Presented at American Conference of Pharmacometrics – November 8-12th, 2021