ArticleCPT: pharmacometrics & systems pharmacology2015
Evaluating the Use of Linear Mixed-Effect Models for Inference of the Concentration-QTc Slope Estimate as a Surrogate for a Biological QTc Model.
Article in CPT: pharmacometrics & systems pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Evaluation of the Effect of Contezolid (MRX-I) on the Corrected QT Interval in a Randomized, Double-Blind, Placebo- and Positive-Controlled Crossover Study in Healthy Chinese Volunteers.Antimicrobial agents and chemotherapy · 2020Trial
- Assessing QT/QTc interval prolongation with concentration-QT modeling for Phase I studies: impact of computational platforms, model structures and confidence interval calculation methods.Journal of pharmacokinetics and pharmacodynamics · 2018Trial
- Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.Anti-cancer drugs · 2018Trial
- Concentration-QTc analysis of quizartinib in patients with relapsed/refractory acute myeloid leukemia.Cancer chemotherapy and pharmacology · 2021Article
- Evaluation of QT Liability for PF-05251749 in the Presence of Potential Circadian Rhythm Modification.CPT: pharmacometrics & systems pharmacology · 2020Article
- Concentration-QT Modeling Following Inhalation of the Novel Inhaled Phosphodiesterase-4 Inhibitor CHF6001 in Healthy Volunteers Shows an Absence of QT Prolongation.CPT: pharmacometrics & systems pharmacology · 2019Article
- Talazoparib has no clinically relevant effect on QTc interval in patients with advanced solid tumors.Anti-cancer drugs · 2019Article
- Model-Informed Drug Development for Ixazomib, an Oral Proteasome Inhibitor.Clinical pharmacology and therapeutics · 2019Review
- Scientific white paper on concentration-QTc modeling.Journal of pharmacokinetics and pharmacodynamics · 2018Review
- Evaluating cardiac risk: exposure response analysis in early clinical drug development.Drug, healthcare and patient safety · 2018Review
- Estimation of QT interval prolongation through model-averaging.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- Systems Chronotherapeutics.Pharmacological reviews · 2017Review
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Authors and funding
2 authors.
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Abstract
In concentration-QTc modeling, oscillatory functions have been used to characterize biological rhythms in QTc profiles. Fitting such functions is not always feasible because it requires sufficient electrocardiograph sampling. In this study, drug concentration and QTc data were simulated using a published biological QTc model (oscillatory functions). Then, linear mixed-effect models and the biological model were fitted and evaluated in terms of biases, precisions, and qualities of inferences. The simpler linear mixed-effect model with day and time as a factor variables provided similar accuracy of the concentration-QTc slope estimates to the complex biological model and was able to accurately predict the drug-induced QTc prolongation with less than 1 ms bias, despite its empirical nature to account for biological rhythm. The current study may guide a concentration-QTc modeling strategy that can be easily prespecified, does not suffer from poor convergence, and achieves little bias in drug-induced QTc estimates.
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