ArticlePLoS computational biology2020
Optimizing circadian drug infusion schedules towards personalized cancer chronotherapy.
Article in PLoS computational biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Radiation chronotherapy-clinical impact of treatment time-of-day: a systematic review.Journal of neuro-oncology · 2019Pooled it
- Circadian rhythm disruption by PARP inhibitors correlates with treatment toxicity in patients with ovarian cancer and is a predictor of side effects.EBioMedicine · 2025Trial
- Chronotherapy in Oncology: Aligning Cancer Treatment with Biological Time.Journal of personalized medicine · 2026Review
- Temporal dynamics in cancer immunotherapy: the interplay between circadian rhythms, tumor microenvironment, and immune checkpoint blockade.Journal of the National Cancer Center · 2026Review
- Magnetic Induction Heating Enables On-Demand Drug Release via Diels-Alder Polymeric Nanocarriers.Biomacromolecules · 2025Article
- Rhythm is essential: Unraveling the relation between the circadian clock and cancer.Critical reviews in oncology/hematology · 2025Review
- Chronopharmacology of AAV gene therapy in mice.microPublication biology · 2025Article
- Circadian rhythms and cancer: implications for timing in therapy.Discover oncology · 2024Review
- Circadian regulation of sinoatrial nodal cell pacemaking function: Dissecting the roles of autonomic control, body temperature, and local circadian rhythmicity.PLoS computational biology · 2024Article
- Inclusion, reporting and analysis of demographic variables in chronobiology and sleep research.Frontiers in neuroscience · 2024Review
- Modeling the Circadian Control of the Cell Cycle and Its Consequences for Cancer Chronotherapy.Biology · 2023Article
- Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress.Life science alliance · 2023Article
- Timed use of digoxin prevents heart ischemia-reperfusion injury through a REV-ERBα-UPS signaling pathway.Nature cardiovascular research · 2022Article
- Dosing time optimization of antihypertensive medications by including the circadian rhythm in pharmacokinetic-pharmacodynamic models.PLoS computational biology · 2022Article
- An Overview of the Circadian Clock in the Frame of Chronotherapy: From Bench to Bedside.Pharmaceutics · 2022Review
- Circadian rhythms and cancers: the intrinsic links and therapeutic potentials.Journal of hematology & oncology · 2022Review
- Understanding the significance of biological clock and its impact on cancer incidence.Cancer letters · 2022Review
- Exploring the link between chronobiology and drug delivery: effects on cancer therapy.Journal of molecular medicine (Berlin, Germany) · 2021Review
- MYC Ran Up the Clock: The Complex Interplay between MYC and the Molecular Circadian Clock in Cancer.International journal of molecular sciences · 2021Review
- Translating around the clock: Multi-level regulation of post-transcriptional processes by the circadian clock.Cellular signalling · 2021Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Precision medicine requires accurate technologies for drug administration and proper systems pharmacology approaches for patient data analysis. Here, plasma pharmacokinetics (PK) data of the OPTILIV trial in which cancer patients received oxaliplatin, 5-fluorouracil and irinotecan via chronomodulated schedules delivered by an infusion pump into the hepatic artery were mathematically investigated. A pump-to-patient model was designed in order to accurately represent the drug solution dynamics from the pump to the patient blood. It was connected to semi-mechanistic PK models to analyse inter-patient variability in PK parameters. Large time delays of up to 1h41 between the actual pump start and the time of drug detection in patient blood was predicted by the model and confirmed by PK data. Sudden delivery spike in the patient artery due to glucose rinse after drug administration accounted for up to 10.7% of the total drug dose. New model-guided delivery profiles were designed to precisely lead to the drug exposure intended by clinicians. Next, the complete mathematical framework achieved a very good fit to individual time-concentration PK profiles and concluded that inter-subject differences in PK parameters was the lowest for irinotecan, intermediate for oxaliplatin and the largest for 5-fluorouracil. Clustering patients according to their PK parameter values revealed patient subgroups for each drug in which inter-patient variability was largely decreased compared to that in the total population. This study provides a complete mathematical framework to optimize drug infusion pumps and inform on inter-patient PK variability, a step towards precise and personalized cancer chronotherapy.
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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.