ArticleScientific reports2019
On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 87 citations in OpenAlex.
- PK-Informed Microphysiological Systems: From Dynamic Dosing to Quantitative In Vitro-In Vivo Translation.Pharmaceutics · 2026Review
- Cardiac microphysiological systems in cardiovascular research: Construction paradigms, maturation trajectories, and translational frontiers.Bioengineering & translational medicine · 2026Review
- Liver-on-a-Chip (LoC) Models: Case Studies of Academic Platforms and Commercial Products.Molecular pharmaceutics · 2026Review
- Ex vivo drug sensitivity profiling to complement molecular profiling in pediatric precision oncology.NPJ precision oncology · 2026Article
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- Constructing biomimetic microenvironments for liver regeneration.Journal of nanobiotechnology · 2025Review
- Modernizing Preclinical Drug Development: The Role of New Approach Methodologies.ACS pharmacology & translational science · 2025Review
- Advances in human organs-on-chips and applications for drug screening and personalized medicine.Fundamental research · 2025Review
- Development of a Microphysiological System to Model Human Cancer Metastasis From the Colon to the Liver.Biotechnology and bioengineering · 2025Article
- Digital twin-enhanced three-organ microphysiological system for studying drug pharmacokinetics in pregnant women.Frontiers in pharmacology · 2025Article
- Multi-Organ Microphysiological Systems Targeting Specific Organs for Recapitulating Disease Phenotypes via Organ Crosstalk.Small science · 2024Article
- A functional aged human iPSC-cortical neuron model recapitulates Alzheimer's disease, senescence, and the response to therapeutics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- An osteosarcoma-on-a-chip model for studying osteosarcoma matrix-cell interactions and drug responses.Bioactive materials · 2024Article
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- Synthetic living materials in cancer biology.Nature reviews bioengineering · 2023Article
- Organic Electronic Platform for Real-Time Phenotypic Screening of Extracellular-Vesicle-Driven Breast Cancer Metastasis.Advanced healthcare materials · 2023Article
- Development of a human malaria-on-a-chip disease model for drug efficacy and off-target toxicity evaluation.Scientific reports · 2023Article
- The evolving role of investigative toxicology in the pharmaceutical industry.Nature reviews. Drug discovery · 2023Review
- Integrated experimental-computational analysis of a HepaRG liver-islet microphysiological system for human-centric diabetes research.PLoS computational biology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
Functional human-on-a-chip systems hold great promise to enable quantitative translation to in vivo outcomes. Here, we explored this concept using a pumpless heart only and heart:liver system to evaluate the temporal pharmacokinetic/pharmacodynamic (PKPD) relationship for terfenadine. There was a time dependent drug-induced increase in field potential duration in the cardiac compartment in response to terfenadine and that response was modulated using a metabolically competent liver module that converted terfenadine to fexofenadine. Using this data, a mathematical model was developed to predict the effect of terfenadine in preclinical species. Developing confidence that microphysiological models could have a transformative effect on drug discovery, we also tested a previously discovered proprietary AstraZeneca small molecule and correctly determined the cardiotoxic response to its metabolite in the heart:liver system. Overall our findings serve as a guiding principle to future investigations of temporal concentration response relationships in these innovative in vitro models, especially, if validated across multiple time frames, with additional pharmacological mechanisms and molecules representing a broad chemical diversity.
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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.