ArticleJournal of pharmacokinetics and pharmacodynamics2021
Detection and impact of hysteresis when evaluating a drug's QTc effect using concentration-QTc analysis.
Article in Journal of pharmacokinetics and pharmacodynamics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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
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Who cites it
7 citing papers in PubMed.
- Concentration-Response Analysis of the Combination of Pyronaridine and Piperaquine on Corrected QT Interval From a Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults of African Sub-Saharan Origin.Clinical and translational science · 2025Trial
- Practical guide to concentration-QTc modeling: a hands-on tutorial.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Beyond the linear model in concentration-QT analysis.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Beyond the linear model in concentration-QT analysis.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Evaluation of moxifloxacin in canine and non-human primate telemetry assays: Comparison of QTc interval prolongation by timepoint and concentration-QTc analysis.Clinical and translational science · 2021Article
- QTc interval analysis-an ever-evolving endeavor.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early-phase studies quantifying the QTc prolongation potential for a new drug often use linear concentration-QTc (C-QTc) models, assuming no delay between plasma concentrations and QTc changes. However, that assumption is not always correct. The term "hysteresis" has been utilized to describe a time lag present between a measurable concentration and a measurable effect. To detect and quantify hysteresis and its impact on study interpretation, studies with hysteresis of 0.25-4 h were simulated with different doses, half-lives, and sampling schedules in a crossover design. Hysteresis was quantified using a novel method termed exposure-normalized GRI (enGRI), a proposed modification of the Glomb-Ring Index (GRI), to account for delay and magnitude of QTc effects. With realistic sampling, the rate of false negative studies (FN) increased proportionally to the delay, even for delays shorter than 1 h. Using an enGRI threshold (γ) of 2 ms resulted in FN with undetected delay and FN without hysteresis at approximately the same rate. For γ = 2 ms, the specificity of enGRI was > 90% throughout the investigated scenarios. We therefore propose the incorporation of enGRI when interpreting results from C-QTc analysis with the intent of characterizing QTc effects.
Indexed as
Identifiers
33118135What 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.