ArticleCPT: pharmacometrics & systems pharmacology2021
Investigational Treatments for COVID-19 may Increase Ventricular Arrhythmia Risk Through Drug Interactions.
Article in CPT: pharmacometrics & systems pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Recent applications of quantitative systems pharmacology and machine learning models across diseases.Journal of pharmacokinetics and pharmacodynamics · 2022Pooled it
- Developing cardiac biomechanical models beyond the clinic: modeling stressors of daily life.Biomechanics and modeling in mechanobiology · 2025Review
- Application of Quantitative Systems Pharmacology Approaches to Support Pediatric Labeling in Rare Diseases.Handbook of experimental pharmacology · 2025Review
- Cardiotoxicity evaluation of two-drug fixed-dose combination therapy under CiPA: a computational study.Translational and clinical pharmacology · 2024Article
- Cardiac Arrhythmias and Autonomic Dysfunction Associated With COVID-19: A Scientific Statement From the American Heart Association.Circulation · 2024Review
- HPC Framework for Performing in Silico Trials Using a 3D Virtual Human Cardiac Population as Means to Assess Drug-Induced Arrhythmic Risk.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- The potential role of SARS-CoV-2 infection in acute coronary syndrome and type 2 myocardial infarction (T2MI): Intertwining spread.Immunity, inflammation and disease · 2023Review
- In silico assessment on TdP risks of drug combinations under CiPA paradigm.Scientific reports · 2023Article
- Assessment of the proarrhythmic effects of repurposed antimalarials for COVID-19 treatment using a comprehensiveFrontiers in pharmacology · 2023Article
- Review
- Quantitative approaches to drug safety: The 2022 PSP special issue.CPT: pharmacometrics & systems pharmacology · 2022Article
- Metabolic and electrolyte abnormalities as risk factors in drug-induced long QT syndrome.Biophysical reviews · 2022Review
- Assessment of proarrhythmogenic risk for chloroquine and hydroxychloroquine using the CiPA concept.European journal of pharmacology · 2021Article
- COVID-19 associated with pulmonary aspergillosis: A literature review.Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi · 2021Review
- Air Pollution and Cardiac Arrhythmias: From Epidemiological and Clinical Evidences to Cellular Electrophysiological Mechanisms.Frontiers in cardiovascular medicine · 2021Review
- Inflammation as a Risk Factor in Cardiotoxicity: An Important Consideration for Screening During Drug Development.Frontiers in pharmacology · 2021Article
- Review
- Sex differences underlying preexisting cardiovascular disease and cardiovascular injury in COVID-19.Journal of molecular and cellular cardiology · 2020Article
- COVID-19 infection and cardiac arrhythmias.Trends in cardiovascular medicine · 2020Review
Corrections and comments
- Update of
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Many drugs that have been proposed for treatment of coronavirus disease 2019 (COVID-19) are reported to cause cardiac adverse events, including ventricular arrhythmias. In order to properly weigh risks against potential benefits, particularly when decisions must be made quickly, mathematical modeling of both drug disposition and drug action can be useful for predicting patient response and making informed decisions. Here, we explored the potential effects on cardiac electrophysiology of four drugs proposed to treat COVID-19: lopinavir, ritonavir, chloroquine, and azithromycin, as well as combination therapy involving these drugs. Our study combined simulations of pharmacokinetics (PKs) with quantitative systems pharmacology (QSP) modeling of ventricular myocytes to predict potential cardiac adverse events caused by these treatments. Simulation results predicted that drug combinations can lead to greater cellular action potential prolongation, analogous to QT prolongation, compared with drugs given in isolation. The combination effect can result from both PK and pharmacodynamic drug interactions. Importantly, simulations of different patient groups predicted that women with pre-existing heart disease are especially susceptible to drug-induced arrhythmias, compared with diseased men or healthy individuals of either sex. Statistical analysis of population simulations revealed the molecular factors that make certain women with heart failure especially susceptible to arrhythmias. Overall, the results illustrate how PK and QSP modeling may be combined to more precisely predict cardiac risks of COVID-19 therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.