ReviewCurrent pharmacology reports
Top-down, Bottom-up and Middle-out Strategies for Drug Cardiac Safety Assessment via Modeling and Simulations.
Review in Current pharmacology reports. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 32 citations in OpenAlex.
- Exploiting Pharmacokinetic/Pharmacodynamic Methods for Optimizing and Accelerating Drug Development of Innovative Anti-Infectives.ChemMedChem · 2026Review
- A Dose-Aware Model for Revealing Dose-Risk Relationship of Drug-Drug Interaction.CPT: pharmacometrics & systems pharmacology · 2025Article
- Artificial intelligence and systems biology analysis in stem cell research and therapeutics development.Stem cells translational medicine · 2025Review
- A Combination of Machine Learning and PBPK Modeling Approach for Pharmacokinetics Prediction of Small Molecules in Humans.Pharmaceutical research · 2024Review
- Review
- Review
- Integrated Use of In Vitro and In Vivo Information for Comprehensive Prediction of Drug Interactions Due to Inhibition of Multiple CYP Isoenzymes.Clinical pharmacokinetics · 2023Article
- In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part III.International journal of molecular sciences · 2023Article
- Physiologically-Based Pharmacokinetic Modelling of Entrectinib Parent and Active Metabolite to Support Regulatory Decision-Making.European journal of drug metabolism and pharmacokinetics · 2021Article
- Early Survival Prediction Framework in CD19-Specific CAR-T Cell Immunotherapy Using a Quantitative Systems Pharmacology Model.Cancers · 2021Article
- Mechanistic Modelling Identifies and Addresses the Risks of Empiric Concentration-Guided Sorafenib Dosing.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Current Approaches and Techniques in Physiologically Based Pharmacokinetic (PBPK) Modelling of Nanomaterials.Nanomaterials (Basel, Switzerland) · 2020Review
- Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for valproic acid and divalproex.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018Article
- On the analysis of complex biological supply chains: From Process Systems Engineering to Quantitative Systems Pharmacology.Computers & chemical engineering · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cardiac safety is an issue causing early terminations at various stages of drug development. Efforts are put into the elimination of false negatives as well as false positives resulting from the current testing paradigm. In silico approaches offer mathematical system and data description from the ion current, through cardiomyocytes level, up to incorporation of inter-individual variability at the population level. The article aims to review three main modelling and simulation approaches, i.e. "top-down" which refers to models built on the observed data, "bottom-up", which stands for a mechanistic description of human physiology, and "middle-out" which combines both strategies. Modelling and simulation is a well-established tool in the assessment of drug proarrhythmic potency with an impact on research and development as well as on regulatory decisions, and it is certainly here to stay. What is more, the shift to systems biology and physiology-based models makes the cardiac effect more predictable.
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.