ArticleBioscience reports2016
Unravelling the complex drug-drug interactions of the cardiovascular drugs, verapamil and digoxin, with P-glycoprotein.
Article in Bioscience reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 47 citations in OpenAlex.
- Pharmacokinetic interactions of esaxerenone with amlodipine and digoxin in healthy Japanese subjects.BMC pharmacology & toxicology · 2020Trial
- Elucidating the Complex Structural and Molecular Mechanisms Driving P-Glycoprotein-Mediated Transport of Cardiac Glycosides.International journal of molecular sciences · 2025Article
- Allosteric Inhibition of P-Glycoprotein-Mediated Efflux by DMH1.Biomedicines · 2025Article
- Applicability of MDR1 Overexpressing Abcb1KO-MDCKII Cell Lines for Investigating In Vitro Species Differences and Brain Penetration Prediction.Pharmaceutics · 2024Article
- Drug-Induced Conformational Dynamics of P-Glycoprotein Underlies the Transport of Camptothecin Analogs.International journal of molecular sciences · 2023Article
- Advantages and potential limitations of applying AFM kymograph analysis to pharmaceutically relevant membrane proteins in lipid bilayers.Scientific reports · 2023Article
- Four Decades of Cytochrome P450 2B Research: From Protein Adducts to Protein Structures and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Digoxin Derivatives Sensitize aJournal of fungi (Basel, Switzerland) · 2022Article
- Structure-based alteration of tryptophan residues of the multidrug transporter CmABCB1 to assess substrate binding using fluorescence spectroscopy.Protein science : a publication of the Protein Society · 2022Article
- NMR Characterization of the Interactions Between Glycosaminoglycans and Proteins.Frontiers in molecular biosciences · 2021Review
- A Mechanistic, Enantioselective, Physiologically Based Pharmacokinetic Model of Verapamil and Norverapamil, Built and Evaluated for Drug-Drug Interaction Studies.Pharmaceutics · 2020Article
- The effects of anthracycline drugs on the conformational distribution of mouse P-glycoprotein explains their transport rate differences.Biochemical pharmacology · 2020Article
- Beta-blocker Use in Moderate and Severe Chronic Obstructive Pulmonary Disease.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2019Article
- The conformation and dynamics of P-glycoprotein in a lipid bilayer investigated by atomic force microscopy.Biochemical pharmacology · 2018Article
- A Conformationally Gated Model of Methadone and Loperamide Transport by P-Glycoprotein.Journal of pharmaceutical sciences · 2018Article
- Boosted coupling of ATP hydrolysis to substrate transport upon cooperative estradiol-17-β-D-glucuronide binding in a Drosophila ATP binding cassette type-C transporter.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Drug Transport at the Brain and Endothelial Dysfunction in Preeclampsia: Implications and Perspectives.Frontiers in physiology · 2018Article
- The roles of cytochrome P450 and P-glycoprotein in the pharmacokinetics of florfenicol in chickens.Iranian journal of veterinary research · 2018Article
- LUCS (Light-Up Cell System), a universal high throughput assay for homeostasis evaluation in live cells.Scientific reports · 2017Article
- Insights Into the Molecular Mechanism of Triptan Transport by P-glycoprotein.Journal of pharmaceutical sciences · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Drug-drug interactions (DDIs) and associated toxicity from cardiovascular drugs represents a major problem for effective co-administration of cardiovascular therapeutics. A significant amount of drug toxicity from DDIs occurs because of drug interactions and multiple cardiovascular drug binding to the efflux transporter P-glycoprotein (Pgp), which is particularly problematic for cardiovascular drugs because of their relatively low therapeutic indexes. The calcium channel antagonist, verapamil and the cardiac glycoside, digoxin, exhibit DDIs with Pgp through non-competitive inhibition of digoxin transport, which leads to elevated digoxin plasma concentrations and digoxin toxicity. In the present study, verapamil-induced ATPase activation kinetics were biphasic implying at least two verapamil-binding sites on Pgp, whereas monophasic digoxin activation of Pgp-coupled ATPase kinetics suggested a single digoxin-binding site. Using intrinsic protein fluorescence and the saturation transfer double difference (STDD) NMR techniques to probe drug-Pgp interactions, verapamil was found to have little effect on digoxin-Pgp interactions at low concentrations of verapamil, which is consistent with simultaneous binding of the drugs and non-competitive inhibition. Higher concentrations of verapamil caused significant disruption of digoxin-Pgp interactions that suggested overlapping and competing drug-binding sites. These interactions correlated to drug-induced conformational changes deduced from acrylamide quenching of Pgp tryptophan fluorescence. Also, Pgp-coupled ATPase activity kinetics measured with a range of verapamil and digoxin concentrations fit well to a DDI model encompassing non-competitive and competitive inhibition of digoxin by verapamil. The results and previous transport studies were combined into a comprehensive model of verapamil-digoxin DDIs encompassing drug binding, ATP hydrolysis, transport and conformational changes.
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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.