ArticleThe Journal of pharmacology and experimental therapeutics2018
Hydroxychloroquine: A Physiologically-Based Pharmacokinetic Model in the Context of Cancer-Related Autophagy Modulation.
Article in The Journal of pharmacology and experimental therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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
52 citing papers in PubMed, 81 citations in OpenAlex.
- Article
- cGAS-IFN-I responses by extracting nuclear DNA from dying cells via nucleocytosis.Nature communications · 2026Article
- Chronic intermittent hypoxia drives M1 macrophage polarization in dorsal root ganglia.Brain, behavior, and immunity · 2025Article
- Safety of Hydroxychloroquine: What a Dermatologist Should Know.American journal of clinical dermatology · 2025Review
- Chitosan-Zinc-Ligated Hydroxychloroquine: Molecular Docking, Synthesis, Characterization, and Trypanocidal Activity againstPolymers · 2024Article
- Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy.Pharmaceutics · 2024Review
- HPC Framework for Performing in Silico Trials Using a 3D Virtual Human Cardiac Population as Means to Assess Drug-Induced Arrhythmic Risk.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Sensitivity of osteosarcoma cell lines to autophagy inhibition as determined by pharmacologic and genetic manipulation.Veterinary and comparative oncology · 2023Article
- The In Vitro, In Vivo, and PBPK Evaluation of a Novel Lung-Targeted Cardiac-Safe Hydroxychloroquine Inhalation Aerogel.AAPS PharmSciTech · 2023Article
- Synergistic Effect of Zinc-Chitosan Nanoparticles and Hydroxychloroquine to Inhibit Buffalo Coronavirus.Polymers · 2023Article
- Chloroquine and Hydroxychloroquine, as Proteasome Inhibitors, Upregulate the Expression and Activity of Organic Anion Transporter 3.Pharmaceutics · 2023Article
- Predicting Hydroxychloroquine Clearance in Healthy and Diseased Populations Using a Physiologically Based Pharmacokinetic Approach.Pharmaceutics · 2023Article
- Tissue- and cell-expression of druggable host proteins provide insights into repurposing drugs for COVID-19.Clinical and translational science · 2022Review
- Physiologically-Based Pharmacokinetics Modeling for Hydroxychloroquine as a Treatment for Malaria and Optimized Dosing Regimens for Different Populations.Journal of personalized medicine · 2022Article
- Pulmonary Delivery of Aerosolized Chloroquine and Hydroxychloroquine to Treat COVID-19: In Vitro Experimentation to Human Dosing Predictions.The AAPS journal · 2022Article
- QTc-interval prolongation and increased risk of sudden cardiac death associated with hydroxychloroquine.European journal of preventive cardiology · 2022Article
- Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis.Arthritis research & therapy · 2022Article
- Translational Modeling of Chloroquine and Hydroxychloroquine Dosimetry in Human Airways for Treating Viral Respiratory Infections.Pharmaceutical research · 2022Article
- Inhibiting Cytoprotective Autophagy in Cancer Therapy: An Update on Pharmacological Small-Molecule Compounds.Frontiers in pharmacology · 2022Review
- Molecular Networking for Drug Toxicities Studies: The Case of Hydroxychloroquine in COVID-19 Patients.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Hydroxychloroquine (HCQ) is a lysosomotropic autophagy inhibitor being used in over 50 clinical trials either alone or in combination with chemotherapy. Pharmacokinetic (PK) and pharmacodynamic (PD) studies with HCQ have shown that drug exposure in the blood does not correlate with autophagy inhibition in either peripheral blood mononuclear cells or tumor tissue. To better explain this PK/PD disconnect, a PBPK was developed for HCQ describing the tissue-specific absorption, distribution, metabolism, and excretion as well as lysosome-specific sequestration. Using physiologic and biochemical parameters derived from literature or obtained experimentally, the model was first developed and validated in mice, and then adapted to simulate human HCQ exposure in whole blood and urine through allometric scaling and species-specific parameter modification. The human model accurately simulated average steady-state concentrations (Css) of those observed in five different HCQ combination clinical trials across seven different doses, which was then expanded by comparison of the Css distribution in a virtual human population at this range of doses. Value of this model lies in its ability to simulate HCQ PK in patients while accounting for PK modification by combination treatment modalities, drug concentrations at the active site in the lysosome under varying pH conditions, and exposure in tissues where toxicity is observed.
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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.