ArticleInternational journal of antimicrobial agents2020
Excessive lysosomal ion-trapping of hydroxychloroquine and azithromycin.
Article in International journal of antimicrobial agents, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Exploring the long-term hydroxychloroquine's effects on COVID-19 outcomes in patients with autoimmune diseases: a systematic review and meta-analysis.European journal of clinical pharmacology · 2026Pooled it
- Immunosuppression by hydroxychloroquine: mechanistic proof in in vitro experiments but limited systemic activity in a randomized placebo-controlled clinical pharmacology study.Immunologic research · 2023Trial
- Cepharanthine inhibits lysosomes and induces apoptosis in triple‑negative breast cancer cells.Molecular medicine reports · 2026Article
- Pharmacokinetics of Lekethromycin in Swine Following Intramuscular Administration at Different Doses with a Single Intravenous Reference Dose for Absolute Bioavailability and Matrix Comparison.Veterinary sciences · 2026Article
- Drug Design and Delivery for Intracellular Bacteria: Emerging Paradigms.Drug development research · 2025Review
- Bioactive polymers as stimulus-responsive anti-metastatic combination agents to treat pancreatic cancer.Biomaterials · 2025Article
- A NewPharmaceuticals (Basel, Switzerland) · 2025Article
- Use of a Double-Transfected System to Predict hOCT2/hMATE1-Mediated Renal Drug-Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Deciphering the immunological interactions: targeting preeclampsia with Hydroxychloroquine's biological mechanisms.Frontiers in pharmacology · 2024Review
- Use of Clearance Concepts to Simulate Impact of Interleukin-6 on Drug Elimination Governed by Cytochromes P450 3A4 and Glomerular Filtration Rate.European journal of drug metabolism and pharmacokinetics · 2023Article
- Inherent Fluorescence Demonstrates Immunotropic Properties for Novel Janus Kinase 3 Inhibitors.ACS pharmacology & translational science · 2023Article
- Magic bullets, magic shields, and antimicrobials in between.Pharmaceutical science advances · 2023Review
- Altered Lysosomal Function Manipulates Cellular Biosynthetic Capacity By Remodeling Intracellular Cholesterol Distribution.Cell biochemistry and biophysics · 2023Article
- Physiologically Based Modelling Framework for Prediction of Pulmonary Pharmacokinetics of Antimicrobial Target Site Concentrations.Clinical pharmacokinetics · 2022Article
- COVID-19 Infection in Rheumatic Patients on Chronic Antimalarial Drugs: A Systematic Review and Meta-Analysis.Journal of clinical medicine · 2022Review
- A Capillary Electrophoresis-Based Method for the Measurement of Hydroxychloroquine and Its Active Metabolite Desethyl Hydroxychloroquine in Whole Blood in Patients with Rheumatoid Arthritis.Molecules (Basel, Switzerland) · 2022Article
- Effect of chronic hydroxychloroquine use on COVID-19 risk in patients with rheumatoid arthritis and systemic lupus erythematosus: a multicenter retrospective cohort.The Journal of international medical research · 2022Article
- Pulmonary Delivery of Aerosolized Chloroquine and Hydroxychloroquine to Treat COVID-19: In Vitro Experimentation to Human Dosing Predictions.The AAPS journal · 2022Article
- Translational Modeling of Chloroquine and Hydroxychloroquine Dosimetry in Human Airways for Treating Viral Respiratory Infections.Pharmaceutical research · 2022Article
- Scoping insight on antiviral drugs against COVID-19.Arabian journal of chemistry · 2021Review
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A recent report identified significant reductions or disappearance of viral load in COVID-19 patients given a combination of hydroxychloroquine and azithromycin. The present communication discusses some common pharmacokinetic properties of these two drugs that may be linked to a potential underlying mechanism of action for these antiviral effects. The physicochemical properties of both hydroxychloroquine and azithromycin are consistent with particularly high affinity for the intracellular lysosomal space, which has been implicated as a target site for antiviral activity. The properties of both drugs predict dramatic accumulation in lysosomes, with calculated lysosomal drug concentrations that exceed cytosolic and extracellular concentrations by more than 50 000-fold. These predictions are consistent with previously reported experimentally measured cellular and extracellular concentrations of azithromycin. This is also reflected in the very large volumes of distribution of these drugs, which are among the highest of all drugs currently in use. The combination of hydroxychloroquine and azithromycin produces very high local concentrations in lysosomes. The clinical significance of this observation is unclear; however, the magnitude of this mechanism of drug accumulation via ion-trapping in lysosomes could be an important factor for the pharmacodynamic effects of this drug combination.
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Registered trials
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