ArticleJournal of pharmacokinetics and pharmacodynamics2018
Physiologically based pharmacokinetic-quantitative systems toxicology and safety (PBPK-QSTS) modeling approach applied to predict the variability of amitriptyline pharmacokinetics and cardiac safety in populations and in individuals.
Article in Journal of pharmacokinetics and pharmacodynamics, 2018. 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
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Who cites it
6 citing papers in PubMed, 19 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling of Antidepressants: A Scoping Review of Existing Models, Applications, and Software Tools.Clinical pharmacokinetics · 2026Article
- Quantitative systems toxicology: modelling to mechanistically understand and predict drug safety.Nature reviews. Drug discovery · 2026Review
- Pharmacological considerations for next-generation protein therapeutics in cardiovascular disease.The Journal of pharmacology and experimental therapeutics · 2025Review
- The evolving role of investigative toxicology in the pharmaceutical industry.Nature reviews. Drug discovery · 2023Review
- Pharmacogenomics and Drug-Induced Phenoconversion Informed Medication Safety Review in the Management of Pain Control and Quality of Life: A Case Report.Journal of personalized medicine · 2022Article
- New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids.Archives of toxicology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The physiologically based pharmacokinetic (PBPK) models allow for predictive assessment of variability in population of interest. One of the future application of PBPK modeling is in the field of precision dosing and personalized medicine. The aim of the study was to develop PBPK model for amitriptyline given orally, predict the variability of cardiac concentrations of amitriptyline and its main metabolite-nortriptyline in populations as well as individuals, and simulate the influence of those xenobiotics in therapeutic and supratherapeutic concentrations on human electrophysiology. The cardiac effect with regard to QT and RR interval lengths was assessed. The Emax model to describe the relationship between amitriptyline concentration and heart rate (RR) length was proposed. The developed PBPK model was used to mimic 29 clinical trials and 19 cases of amitriptyline intoxication. Three clinical trials and 18 cases were simulated with the use of PBPK-QSTS approach, confirming lack of cardiotoxic effect of amitriptyline in therapeutic doses and the increase in heart rate along with potential for arrhythmia development in case of amitriptyline overdose. The results of our study support the validity and feasibility of the PBPK-QSTS modeling development for personalized medicine.
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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.