ArticleCPT: pharmacometrics & systems pharmacology2014
Interaction Between Domperidone and Ketoconazole: Toward Prediction of Consequent QTc Prolongation Using Purely In Vitro Information.
Article in CPT: pharmacometrics & systems pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Simultaneous Ivabradine Parent-Metabolite PBPK/PD Modelling Using a Bayesian Estimation Method.The AAPS journal · 2020Trial
- Beyond homogeneity: Assessing the validity of the Michaelis-Menten rate law in spatially heterogeneous environments.PLoS computational biology · 2024Article
- Beyond the Michaelis-Menten: Accurate Prediction of In Vivo Hepatic Clearance for Drugs With Low KClinical and translational science · 2020Article
- Integrating in vitro data and physiologically based kinetic modeling-facilitated reverse dosimetry to predict human cardiotoxicity of methadone.Archives of toxicology · 2020Article
- Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology.Journal of clinical medicine · 2019Review
- Cardiovascular disease models: A game changing paradigm in drug discovery and screening.Biomaterials · 2019Review
- Quantitative systems toxicology.Current opinion in toxicology · 2017Article
- Humans Vary, So Cardiac Models Should Account for That Too!Frontiers in physiology · 2017Review
- Pharmacokinetic-pharmacodynamic modelling of drug-induced QTc interval prolongation in man: prediction from in vitro human ether-à-go-go-related gene binding and functional inhibition assays and conscious dog studies.British journal of pharmacology · 2016Article
- How computer simulations of the human heart can improve anti-arrhythmia therapy.The Journal of physiology · 2016Review
- The promises of quantitative systems pharmacology modelling for drug development.Computational and structural biotechnology journal · 2016Review
- Early Drug Discovery Prediction of Proarrhythmia Potential and Its Covariates.The AAPS journal · 2015Article
- Modeling and Simulation Approaches for Cardiovascular Function and Their Role in Safety Assessment.CPT: pharmacometrics & systems pharmacology · 2015Review
- Predicting QTc Prolongation in Man From Only In Vitro Data.CPT: pharmacometrics & systems pharmacology · 2014Article
- Top-down, Bottom-up and Middle-out Strategies for Drug Cardiac Safety Assessment via Modeling and Simulations.Current pharmacology reportsReview
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We aimed to investigate the application of combined mechanistic pharmacokinetic (PK) and pharmacodynamic (PD) modeling and simulation in predicting the domperidone (DOM) triggered pseudo-electrocardiogram modification in the presence of a CYP3A inhibitor, ketoconazole (KETO), using in vitro-in vivo extrapolation. In vitro metabolic and inhibitory data were incorporated into physiologically based pharmacokinetic (PBPK) models within Simcyp to simulate time course of plasma DOM and KETO concentrations when administered alone or in combination with KETO (DOM+KETO). Simulated DOM concentrations in plasma were used to predict changes in gender-specific QTcF (Fridericia correction) intervals within the Cardiac Safety Simulator platform taking into consideration DOM, KETO, and DOM+KETO triggered inhibition of multiple ionic currents in population. Combination of in vitro-in vivo extrapolation, PBPK, and systems pharmacology of electric currents in the heart was able to predict the direction and magnitude of PK and PD changes under coadministration of the two drugs although some disparities were detected.
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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.