Trial reportBritish journal of pharmacology2017
Predicting QRS and PR interval prolongations in humans using nonclinical data.
Trial report in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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
6 citing papers in PubMed, 15 citations in OpenAlex.
- Predicting QRS and PR interval prolongations in humans using nonclinical data.British journal of pharmacology · 2017Trial
- QT Myopia and Cardiac Safety: Expanding the Aperture of Arrhythmia Assessment in Early Phase Drug Development.Clinical and translational science · 2026Review
- An overview of drug-induced sodium channel blockade and changes in cardiac conduction: Implications for drug safety.Clinical and translational science · 2024Review
- Cardiac sodium channel inhibition by lamotrigine: In vitro characterization and clinical implications.Clinical and translational science · 2022Article
- Computational translation of drug effects from animal experiments to human ventricular myocytes.Scientific reports · 2020Article
- A tutorial on model informed approaches to cardiovascular safety with focus on cardiac repolarisation.Journal of pharmacokinetics and pharmacodynamics · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeRisk of cardiac conduction slowing (QRS/PR prolongations) is assessed prior to clinical trials using in vitro and in vivo studies. Understanding the quantitative translation of these studies to the clinical situation enables improved risk assessment in the nonclinical phase. EXPERIMENTAL APPROACH: Four compounds that prolong QRS and/or PR (AZD1305, flecainide, quinidine and verapamil) were characterized using in vitro (sodium/calcium channels), in vivo (guinea pigs/dogs) and clinical data. Concentration-matched translational relationships were developed based on in vitro and in vivo modelling, and the in vitro to clinical translation of AZD1305 was quantified using an in vitro model. KEY
resultsMeaningful (10%) human QRS/PR effects correlated with low levels of in vitro Na CONCLUSION AND IMPLICATIONS: Small changes in vitro and in vivo consistently translated to meaningful PR/QRS changes in humans across compounds. Assuming broad applicability of these approaches to assess cardiovascular safety risk for non-arrhythmic drugs, this study provides a means of predicting human QRS/PR effects of new drugs from effects observed in nonclinical studies.
Indexed as
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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.