4.7 Article

Mathematical Modeling of Remdesivir to Treat COVID-19: Can Dosing Be Optimized?

Related references

Note: Only part of the references are listed.
Article Statistics & Probability

Robust analogs to the coefficient of variation

Chandima N. P. G. Arachchige et al.

Summary: This study explores the feasibility of using quantile-based measures of relative dispersion as an alternative to the coefficient of variation (CV). The findings suggest that using the interquartile range or the median absolute deviation as robust estimators can yield similar results to the CV, with better robustness to outliers and skewed distributions.

JOURNAL OF APPLIED STATISTICS (2022)

Article Medicine, General & Internal

Patient Trajectories Among Persons Hospitalized for COVID-19 A Cohort Study

Brian T. Garibaldi et al.

Summary: This study investigated factors predictive of severe COVID-19 disease or death in patients upon hospital admission, finding that age, nursing home residence, comorbid conditions, obesity, respiratory symptoms, respiratory rate, fever, absolute lymphocyte count, etc. are strongly associated with disease progression.

ANNALS OF INTERNAL MEDICINE (2021)

Editorial Material Immunology

Emerging RNA-Dependent RNA Polymerase Mutation in a Remdesivir-Treated B-cell Immunodeficient Patient With Protracted Coronavirus Disease 2019

Martin Martinot et al.

Summary: A 76-year-old female with post-rituximab B-cell immuno-deficiency and persistent SARS-CoV-2 viremia developed a mutation in RdRP (D484Y) following treatment with remdesivir, but was successfully cured after supplementation with convalescent plasma.

CLINICAL INFECTIOUS DISEASES (2021)

Article Microbiology

Off-Target In Vitro Profiling Demonstrates that Remdesivir Is a Highly Selective Antiviral Agent

Yili Xu et al.

Summary: Remdesivir is the first FDA-approved antiviral for COVID-19 treatment, with broad-spectrum activity against various coronaviruses. Studies have shown low off-target toxicity in cellular assays, indicating a favorable safety profile.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Review Pharmacology & Pharmacy

Challenges of drug development during the COVID-19 pandemic: Key considerations for clinical trial designs

Jun Shi et al.

Summary: This article focuses on translational science principles and strategies for conducting clinical trials in a pandemic in order to expedite the development and approval of COVID-19 therapies.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2021)

Article Medicine, Research & Experimental

Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection

Vanessa Monteil et al.

Summary: The combination therapy of remdesivir with recombinant soluble ACE2 shows significant therapeutic effects against SARS-CoV-2 in both cell and kidney organoid models. By targeting two different modalities of the virus's life cycle, this approach improves therapeutic windows. The study lays the groundwork for investigating combinatorial regimens in future COVID-19 clinical trials.

EMBO MOLECULAR MEDICINE (2021)

Article Medicine, General & Internal

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

A. C. Kalil et al.

Summary: Combination treatment with baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Multidisciplinary Sciences

High-throughput rational design of the remdesivir binding site in the RdRp of SARS-CoV-2: implications for potential resistance

Aditya K. Padhi et al.

Summary: With the use of mutational mapping, it was predicted that only a few mutations in the nsp12 subunit of RdRp are needed for SARS-CoV-2 to develop resistance to remdesivir. Certain mutations resulted in decreased binding affinity to remdesivir, indicating drug resistance. Identifying potential hotspot residues prone to mutation improves our understanding of SARS-CoV-2 drug resistance and COVID-19 pathogenesis.

ISCIENCE (2021)

Review Medicine, General & Internal

Major Update: Remdesivir for Adults With COVID-19: A Living Systematic Review and Meta-analysis for the American College of Physicians Practice Points

Anjum S. Kaka et al.

Summary: The study suggests that remdesivir may not significantly reduce mortality in COVID-19 patients, but it likely improves the percentage of patients who recover and reduces serious harms. It may also result in a small decrease in the proportion of patients needing ventilation.

ANNALS OF INTERNAL MEDICINE (2021)

Article Multidisciplinary Sciences

Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort

Nadege Neant et al.

Summary: The study found that age ≥ 65 years, male gender, and chronic pulmonary disease were risk factors associated with mortality from COVID-19. Viral dynamics post-infection independently predicted mortality risk, and pharmacological interventions could shorten time to viral clearance, reducing mortality rates.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Review Pharmacology & Pharmacy

Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of Remdesivir, a SARS-CoV-2 Replication Inhibitor

Rita Humeniuk et al.

Summary: Remdesivir is an approved treatment for severe COVID-19 in adults and children, with a dosing regimen based on pharmacokinetic and safety evaluations. Predictions suggest low potential for drug-drug interactions and efficient conversion to the active form for effective treatment.

CLINICAL PHARMACOKINETICS (2021)

Article Virology

Remdesivir for the treatment of Covid-19: the value of biochemical studies

Matthias Gotte

Summary: Remdesivir is the only FDA-approved antiviral small molecule for treating SARS-CoV-2 infection, targeting the viral RNA-dependent RNA polymerase to inhibit viral replication. Its antiviral effects in cell cultures, animal models, and reduction of viral load in patients make it a benchmark for future drug development efforts aiming at orally available treatments.

CURRENT OPINION IN VIROLOGY (2021)

Article Immunology

Viral Load Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Individuals With Coronavirus Disease 2019

James Regan et al.

Summary: The dynamics of SARS-CoV-2 remain understudied, but early systemic seeding of the virus was observed in hospitalized individuals. Remdesivir treatment was associated with faster viral decay in the body.

OPEN FORUM INFECTIOUS DISEASES (2021)

Article Microbiology

Global Genomic Analysis of SARS-CoV-2 RNA Dependent RNA Polymerase Evolution and Antiviral Drug Resistance

Alfredo Mari et al.

Summary: Various antiviral treatments for COVID-19, including repurposed drugs, have been investigated. The RNA-dependent RNA polymerase of SARS-CoV-2 has been targeted by inhibitors like remdesivir, but potential resistance mutations are rare and unlikely to destabilize the polymerase. This suggests that monitoring for drug resistance during the pandemic is crucial for global efforts.

MICROORGANISMS (2021)

Article Pharmacology & Pharmacy

A mechanism-based pharmacokinetic model of remdesivir leveraging interspecies scaling to simulate COVID-19 treatment in humans

Patrick O. Hanafin et al.

Summary: The outbreak of SARS-CoV-2 led to the COVID-19 pandemic with millions of confirmed infections and deaths worldwide. Remdesivir has shown effectiveness against coronaviruses, but its distribution to the site of lung infection in humans is unknown. Alternative dosing strategies may be needed to achieve more efficacious concentrations in human lungs.

CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY (2021)

Article Multidisciplinary Sciences

Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection

Emmie de Wit et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

Article Medicine, General & Internal

Remdesivir for the Treatment of Covid-19-Final Report

John H. Beigel et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Article Medicine, Research & Experimental

Safety, Tolerability, and Pharmacokinetics of Remdesivir, An Antiviral for Treatment of COVID-19, in Healthy Subjects

Rita Humeniuk et al.

CTS-CLINICAL AND TRANSLATIONAL SCIENCE (2020)

Article Chemistry, Physical

Structural Basis of the Potential Binding Mechanism of Remdesivir to SARS-CoV-2 RNA-Dependent RNA Polymerase

Leili Zhang et al.

JOURNAL OF PHYSICAL CHEMISTRY B (2020)

Editorial Material Medicine, Research & Experimental

Safety profile of the antiviral drug remdesivir: An update

Qianqian Fan et al.

BIOMEDICINE & PHARMACOTHERAPY (2020)

Review Infectious Diseases

Influenza and antiviral resistance: an overview

Temi Lampejo

EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES (2020)

Review Medicine, Research & Experimental

Animal to human translation: a systematic scoping review of reported concordance rates

Cathalijn H. C. Leenaars et al.

JOURNAL OF TRANSLATIONAL MEDICINE (2019)

Article Biology

Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models

Desiree Y. Baeder et al.

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES (2016)

Article Biochemistry & Molecular Biology

Translating slow-binding inhibition kinetics into cellular and in vivo effects

Grant K. Walkup et al.

NATURE CHEMICAL BIOLOGY (2015)

Article Cell Biology

Classic reaction kinetics can explain complex patterns of antibiotic action

Pia Abel zur Wiesch et al.

SCIENCE TRANSLATIONAL MEDICINE (2015)

Article Biotechnology & Applied Microbiology

Probing the links between in vitro potency, ADMET and physicochemical parameters

M. Paul Gleeson et al.

NATURE REVIEWS DRUG DISCOVERY (2011)

Article Medicine, General & Internal

Antiviral resistance and the control of pandemic influenza

Marc Lipsitch et al.

PLOS MEDICINE (2007)

Article Multidisciplinary Sciences

Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success

Y. Claire Wang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2006)

Review Immunology

Modelling viral and immune system dynamics

AS Perelson

NATURE REVIEWS IMMUNOLOGY (2002)

Article Pharmacology & Pharmacy

General pharmacokinetic model for drugs exhibiting target-mediated drug disposition

DE Mager et al.

JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS (2001)