ArticleAmerican journal of respiratory and critical care medicine2013
Acceleration of tuberculosis treatment by adjunctive therapy with verapamil as an efflux inhibitor.
Article in American journal of respiratory and critical care medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
- Effect of calcium-channel blockers on the risk of active tuberculosis and mortality: systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- A Dose-Finding Study to Guide Use of Verapamil as an Adjunctive Therapy in Tuberculosis.Clinical pharmacology and therapeutics · 2024Trial
- Impact of rifampicin on P-glycoprotein (ABCB1) expression in M1 and M2 macrophages derived from the THP-1 monocytic cell line or peripheral blood mononuclear cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The host calcium system contributes to intracellularInfection and immunity · 2025Article
- Efflux pumps positively contribute to rifampin resistance in rpoB mutant Mycobacterium tuberculosis.Annals of clinical microbiology and antimicrobials · 2025Article
- A potent phenylalkylamine disrupts mycobacterial membrane bioenergetics and augments bactericidal activity of bedaquiline.iScience · 2025Article
- Host-directed therapy for tuberculosis.European journal of medical research · 2025Review
- Review
- Association Between Diabetes Mellitus-Tuberculosis and the Generation of Drug Resistance.Microorganisms · 2024Review
- Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens.Antibiotics (Basel, Switzerland) · 2024Review
- In vitro and in vivo evaluation of dual Clofazimine and Verapamil loaded PLGA nanoparticles.Indian journal of clinical biochemistry : IJCB · 2023Article
- Mycobacterium tuberculosis Gene Expression Associated With Fluoroquinolone Resistance and Efflux Pump Inhibition.The Journal of infectious diseases · 2023Article
- Redefining tuberculosis: an interview with Lalita Ramakrishnan.Disease models & mechanisms · 2023Article
- Gaucher disease protects against tuberculosis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The human proton pump inhibitors inhibitProceedings of the National Academy of Sciences of the United States of America · 2023Article
- C-1 Substituted isoquinolines potentiate the antimycobacterial activity of rifampicin and ethambutol.Frontiers in antibiotics · 2023Article
- Antibacterial and Antifungal Alkaloids from Asian Angiosperms: Distribution, Mechanisms of Action, Structure-Activity, and Clinical Potentials.Antibiotics (Basel, Switzerland) · 2022Review
- Investigation of the effect of the calcium channel blocker, verapamil, on the parasite burden, inflammatory response and angiogenesis in experimentalFood and waterborne parasitology · 2022Article
- Critical discussion on drug efflux in Mycobacterium tuberculosis.FEMS microbiology reviews · 2022Review
- The Impact of Hypertension and Use of Calcium Channel Blockers on Tuberculosis Treatment Outcomes.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleA major priority in tuberculosis (TB) is to reduce effective treatment times and emergence of resistance. Recent studies in macrophages and zebrafish show that inhibition of mycobacterial efflux pumps with verapamil reduces the bacterial drug tolerance and may enhance drug efficacy.
objectivesUsing mice, a mammalian model known to predict human treatment responses, and selecting conservative human bioequivalent doses, we tested verapamil as an adjunctive drug together with standard TB chemotherapy. As verapamil is a substrate for CYP3A4, which is induced by rifampin, we evaluated the pharmacokinetic/pharmacodynamic relationships of verapamil and rifampin coadministration in mice.
methodsUsing doses that achieve human bioequivalent levels matched to those of standard verapamil, but lower than those of extended release verapamil, we evaluated the activity of verapamil added to standard chemotherapy in both C3HeB/FeJ (which produce necrotic granulomas) and the wild-type background C3H/HeJ mouse strains. Relapse rates were assessed after 16, 20, and 24 weeks of treatment in mice. MEASUREMENTS AND MAIN
resultsWe determined that a dose adjustment of verapamil by 1.5-fold is required to compensate for concurrent use of rifampin during TB treatment. We found that standard TB chemotherapy plus verapamil accelerates bacterial clearance in C3HeB/FeJ mice with near sterilization, and significantly lowers relapse rates in just 4 months of treatment when compared with mice receiving standard therapy alone.
conclusionsThese data demonstrate treatment shortening by verapamil adjunctive therapy in mice, and strongly support further study of verapamil and other efflux pump inhibitors in human TB.
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