Related Experiment Video
Updated: May 20, 2025

Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
Population Pharmacokinetic Modelling of Remdesivir and Its Metabolite GS-441524 in Hospitalised Patients with
Darren M Roberts1,2,3,4, Xin Liu5, Suzanne L Parker5
1The University of Queensland Centre for Clinical Research, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Australia. 1darren1@gmail.com.
Background And Objectives:
There are limited data testing whether the licensed dose of remdesivir and its active metabolite GS-441524 achieve target concentrations in hospitalised patients with confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of coronavirus disease-2019 (COVID-19). The objectives of this study were to describe the population pharmacokinetics of remdesivir and GS-441524 in hospitalised patients treated for COVID-19 and develop a model to inform dose optimisation in clinical use.
Methods:
This was a prospective, open-labelled, multi-centre, observational study in four Australian hospitals in adults with confirmed SARS-CoV-2 infection. Patients were administered the licensed remdesivir dose. Remdesivir and GS-441524 concentrations were quantified in multiple plasma samples at different times in the dosing interval by ultra-high-performance liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Patients were divided into two groups: pharmacokinetic model building and external validation. A population pharmacokinetic analysis was built using non-linear mixed-effects modelling. Monte Carlo simulations were performed to describe the impact of age, kidney function and dosing regimen on drug concentrations.
Results:
In total, 33 patients were enrolled (median age 70 years, estimated glomerular filtration rate (eGFR) 80 mL/min/1.73 m2). The pharmacokinetics for both compounds were adequately described by a two-compartment model (one compartment for each compound) with first-order elimination. Key covariates included in the final model were age and eGFR. GS-441524 plasma concentrations exceeded the lowest reported half-maximal effective concentration (EC50) with the recommended dosage, and higher dosages exceeded the lowest reported 90%-effective concentration (EC90).
Conclusions:
The licensed remdesivir dose may achieve target concentrations of GS-441524, but higher dosages may optimise outcomes. Dose adjustments are guided primarily by kidney function.
More Related Videos
09:17A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii
Published on: January 2, 2017
07:10Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
Published on: January 7, 2019
Related Concept Videos
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion,...
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
One-Compartment Open Model for IV Bolus Administration: Estimation of Elimination Rate Constant, Half-Life and Volume of Distribution
Analysis of Population Pharmacokinetic Data
One-Compartment Open Model for IV Bolus Administration: General Considerations
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...
Compartment Models: Single-Compartment Model