ArticleThe AAPS journal2020
Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy.
Article in The AAPS journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Meta-analysis on outcome-worsening comorbidities of COVID-19 and related potential drug-drug interactions.Pharmacological research · 2020Pooled it
- A Low-cost Fluorescent Sensor Based on N, S-CQDs for the Ratiometric Detection of Azithromycin.Journal of fluorescence · 2026Article
- Nbeal2 Inactivation Triggers Abl1 Stabilisation and Dysregulated Subcellular Localisation of the Multi-Drug-Resistant Protein MDR1 (ABCB1) in Mast Cells.Immunology · 2026Article
- Attenuate host susceptibility to respiratory virus invasion by inhibiting interactions between host proteins SLC16A3 and AP1G1.Microbiology spectrum · 2025Article
- Antihistamines as an early treatment for Covid-19.Heliyon · 2023Article
- Article
- Considerations into pharmacogenomics of COVID-19 pharmacotherapy: Hope, hype and reality.Pulmonary pharmacology & therapeutics · 2022Review
- Involvement of Transporters in Intestinal Drug-Drug Interactions of Oral Targeted Anticancer Drugs Assessed by Changes in Drug Absorption Time.Pharmaceutics · 2022Article
- Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?Pharmaceuticals (Basel, Switzerland) · 2022Review
- Synergistic Adverse Effects of Azithromycin and Hydroxychloroquine on Human Cardiomyocytes at a Clinically Relevant Treatment Duration.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies.Frontiers in pharmacology · 2022Review
- Effect of azithromycin and hydroxychloroquine in patients hospitalized with COVID-19: Network meta-analysis of randomized controlled trials.Journal of medical virology · 2021Article
- Repurposing functional inhibitors of acid sphingomyelinase (fiasmas): an opportunity against SARS-CoV-2 infection?Journal of clinical pharmacy and therapeutics · 2021Review
- Drugs in COVID-19 Clinical Trials: Predicting Transporter-Mediated Drug-Drug Interactions Using In Vitro Assays and Real-World Data.Clinical pharmacology and therapeutics · 2021Article
- Possible Role of ABCB1 in Lysosomal Accumulation of Azithromycin in COVID-19 Therapy.Clinical pharmacology and therapeutics · 2021Article
- Antihistamines and azithromycin as a treatment for COVID-19 on primary health care - A retrospective observational study in elderly patients.Pulmonary pharmacology & therapeutics · 2021Observational
- Review
- An Update on Antiviral Therapy Against SARS-CoV-2: How Far Have We Come?Frontiers in pharmacology · 2021Review
- System biological investigations of hydroxychloroquine and azithromycin targets and their implications in QT interval prolongation.Chemico-biological interactions · 2020Article
- Azithromycin and glucosamine may amplify the type 1 interferon response to RNA viruses in a complementary fashion.Immunology letters · 2020Review
Corrections and comments
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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
The co-administration of hydroxychloroquine with azithromycin is proposed in COVID-19 therapy. We hypothesize a new mechanism supporting the synergistic interaction between these drugs. Azithromycin is a substrate of ABCB1 (P-glycoprotein) which is localized in endosomes and lysosomes with a polarized substrate transport from the cell cytosol into the vesicle interior. SARS-CoV-2 and drugs meet in these acidic organelles and both basic drugs, which are potent lysosomotropic compounds, will become protonated and trapped within these vesicles. Consequently, their intra-vesicular concentrations can attain low micromolar effective cytotoxic concentrations on SARS-CoV-2 while concomitantly increase the intra-vesicular pH up to around neutrality. This last effect inhibits lysosomal enzyme activities responsible in virus entry and replication cycle. Based on these considerations, we hypothesize that ABCB1 could be a possible enhancer by confining azithromycin more extensively than expected when the trapping is solely dependent on the passive diffusion. This additional mechanism may therefore explain the synergistic effect when azithromycin is added to hydroxychloroquine, leading to apparently more rapid virus clearance and better clinical benefit, when compared to monotherapy with hydroxychloroquine alone.
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