ArticleThe AAPS journal2018
Virtual Thorough QT (TQT) Trial-Extrapolation of In Vitro Cardiac Safety Data to In Vivo Situation Using Multi-Scale Physiologically Based Ventricular Cell-wall Model Exemplified with Tolterodine and Fesoterodine.
Article in The AAPS journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- In silico modeling of methadone-related ion current effects to predict QT interval prolongation.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Inhibition of voltage-dependent KThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- How circadian variability of the heart rate and plasma electrolytes concentration influence the cardiac electrophysiology - model-based case study.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- The role of sex, age and genetic polymorphisms of CYP enzymes on the pharmacokinetics of anticholinergic drugs.Pharmacology research & perspectives · 2021Review
- Risk Assessment of Drug-Induced Long QT Syndrome for Some COVID-19 Repurposed Drugs.Clinical and translational science · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
QT interval prolongation typically assessed with dedicated clinical trials called thorough QT/QTc (TQT) studies is used as surrogate to identify the proarrhythmic risk of drugs albeit with criticism in terms of cost-effectiveness in establishing the actual risk of torsade de pointes (TdP). Quantitative systems toxicology and safety (QSTS) models have potential to quantitatively translate the in vitro cardiac safety data to clinical level including simulation of TQT trials. Virtual TQT simulations have been exemplified with use of two related drugs tolterodine and fesoterodine. The impact of bio-relevant concentration in plasma versus estimated heart tissue exposure on predictions was also assessed. Tolterodine and its therapeutically equipotent metabolite formed via CYP2D6 pathway, 5-HMT, inhibit multiple cardiac ion currents (I
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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.