ArticlePharmaceutical research2019
Analyzing the Mechanisms Behind Macrolide Antibiotic-Induced Liver Injury Using Quantitative Systems Toxicology Modeling.
Article in Pharmaceutical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
27 citing papers in PubMed, 63 citations in OpenAlex.
- Quantitative systems toxicology (QST) reproduces species differences in PF-04895162 liver safety due to combined mitochondrial and bile acid toxicity.Pharmacology research & perspectives · 2019Trial
- Quantitative Systems Toxicology Modeling with DILIsym to Support Phase 3 Dose Selection for Fezolinetant.Clinical pharmacology and therapeutics · 2026Article
- Human Leukocyte Antigen (International journal of molecular sciences · 2026Review
- Safety of high-dose dual therapy forFrontiers in pharmacology · 2026Article
- Quantitative Systems Toxicology Predicts Ivacaftor-Induced Oxidative Stress Contributes to CFTR Modulator Hepatotoxicity.Clinical pharmacology and therapeutics · 2026Article
- Drug metabolizing enzymes and transporters, and their roles for the development of drug-induced liver injury.Expert opinion on drug metabolism & toxicology · 2025Review
- Review
- Drug-Induced Liver Injury-Pharmacological Spectrum Among Children.International journal of molecular sciences · 2025Review
- The Advance and Clinical Practice on Lung Disease Caused byInfection and drug resistance · 2025Article
- Article
- Antibiotic Potentiation as a Promising Strategy to Combat Macrolide Resistance in Bacterial Pathogens.Antibiotics (Basel, Switzerland) · 2023Review
- Clarithromycin-induced acute liver injury in a patient with positiveAnnals of medicine and surgery (2012) · 2023Article
- A Phase-I pharmacokinetic, safety and food-effect study on flubentylosin, a novel analog of Tylosin-A having potent anti-Wolbachia and antifilarial activity.PLoS neglected tropical diseases · 2023Article
- The Combination of a Human Biomimetic Liver Microphysiology System with BIOLOGXsym, a Quantitative Systems Toxicology (QST) Modeling Platform for Macromolecules, Provides Mechanistic Understanding of Tocilizumab- and GGF2-Induced Liver Injury.International journal of molecular sciences · 2023Article
- Novel read through agent: ZKN-0013 demonstrates efficacy in APCJournal of molecular medicine (Berlin, Germany) · 2023Article
- Review
- Genome-Wide Association Study of Nucleotide Variants Associated with Resistance to Nine Antimicrobials inMicroorganisms · 2022Article
- Comparing the Liver Safety Profiles of 4 Next-Generation CGRP Receptor Antagonists to the Hepatotoxic CGRP Inhibitor Telcagepant Using Quantitative Systems Toxicology Modeling.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Azithromycin-Induced Liver Injury in an Asthma Exacerbation Patient With Autoimmune Features.Cureus · 2022Article
- Investigating bile acid-mediated cholestatic drug-induced liver injury using a mechanistic model of multidrug resistance protein 3 (MDR3) inhibition.Frontiers in pharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
purposeMacrolide antibiotics are commonly prescribed treatments for drug-resistant bacterial infections; however, many macrolides have been shown to cause liver enzyme elevations and one macrolide, telithromycin, has been pulled from the market by its provider due to liver toxicity. This work seeks to assess the mechanisms responsible for the toxicity of macrolide antibiotics.
methodsFive macrolides were assessed in in vitro systems designed to test for bile acid transporter inhibition, mitochondrial dysfunction, and oxidative stress. The macrolides were then represented in DILIsym, a quantitative systems pharmacology (QST) model of drug-induced liver injury, placing the in vitro results in context with each compound's predicted liver exposure and known biochemistry.
resultsDILIsym results suggest that solithromycin and clarithromycin toxicity is primarily due to inhibition of the mitochondrial electron transport chain (ETC) while erythromycin toxicity is primarily due to bile acid transporter inhibition. Telithromycin and azithromycin toxicity was not predicted by DILIsym and may be caused by mechanisms not currently incorporated into DILIsym or by unknown metabolite effects.
conclusionsThe mechanisms responsible for toxicity can be significantly different within a class of drugs, despite the structural similarity among the drugs. QST modeling can provide valuable insight into the nature of these mechanistic differences.
Indexed as
Identifiers
What OpenQuestion holds
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.