ArticleAntimicrobial agents and chemotherapy2013
Multiscale distribution and bioaccumulation analysis of clofazimine reveals a massive immune system-mediated xenobiotic sequestration response.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 75 citations in OpenAlex.
- Addition of Clofazimine Enhances the Activity of Standard Treatment Regimen in a Mouse Model of Tuberculous Meningitis.The Journal of infectious diseases · 2026Article
- Analytical Method Development and Validation for Clofazimine in Human Plasma and Application of LC-MS/MS Based Methods for Clofazimine and Bedaquiline in Indian MDR-TB Patients Stratified by HIV Coinfection.Journal of mass spectrometry : JMS · 2026Article
- Targeted delivery of antitubercular drugs using glucan lipid particles.Microbiology spectrum · 2025Article
- Anti-Cryptosporidial Drug-Discovery Challenges and Existing Therapeutic Avenues: A "One-Health" Concern.Life (Basel, Switzerland) · 2024Review
- Understanding theFrontiers in parasitology · 2024Review
- Database screening as a strategy to identify endogenous candidate metabolites to probe and assess mitochondrial drug toxicity.Scientific reports · 2023Article
- Advancing Diagnosis and Treatment in People Living with HIV and Tuberculosis Meningitis.Current HIV/AIDS reports · 2023Review
- Quantitative Raman chemical imaging of intracellular drug-membrane aggregates and small molecule drug precipitates in cytoplasmic organelles.Advanced drug delivery reviews · 2023Review
- Distinguishing the Concentration- vs. Bioaccumulation-Dependent Immunological and Metabolic Effects of Clofazimine.Pharmaceutics · 2023Article
- Clofazimine-Mediated, Age-Related Changes in Skeletal Muscle Mitochondrial Metabolites.Metabolites · 2023Article
- Clofazimine for the treatment of tuberculosis.Frontiers in pharmacology · 2023Review
- Respirable Clofazimine Particles Produced by Air Jet Milling Technique Are Efficacious in Treatment of BALB/c Mice with Chronic Mycobacterium tuberculosis Infection.Antimicrobial agents and chemotherapy · 2022Article
- Molecular design of a pathogen activated, self-assembling mechanopharmaceutical device.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- Interleukin-13-Overexpressing Mice Represent an Advanced Preclinical Model for Detecting the Distribution of Antimycobacterial Drugs within Centrally Necrotizing Granulomas.Antimicrobial agents and chemotherapy · 2022Article
- An Adaptive Biosystems Engineering Approach towards Modeling the Soluble-to-Insoluble Phase Transition of Clofazimine.Pharmaceutics · 2021Article
- Quantitative Analysis of the Phase Transition Mechanism Underpinning the Systemic Self-Assembly of a Mechanopharmaceutical Device.Pharmaceutics · 2021Article
- Clofazimine-Loaded Mucoadhesive Nanoparticles Prepared by Flash Nanoprecipitation for Strategic Intestinal Delivery.Pharmaceutical research · 2021Article
- Clofazimine-related duodenal pigmentation.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2021Article
- Activity of Clofazimine and TBI-166 against Mycobacterium tuberculosis in Different Administration Intervals in Mouse Tuberculosis Models.Antimicrobial agents and chemotherapy · 2021Article
- Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chronic exposure to some well-absorbed but slowly eliminated xenobiotics can lead to their bioaccumulation in living organisms. Here, we studied the bioaccumulation and distribution of clofazimine, a riminophenazine antibiotic used to treat mycobacterial infection. Using mice as a model organism, we performed a multiscale, quantitative analysis to reveal the sites of clofazimine bioaccumulation during chronic, long-term exposure. Remarkably, between 3 and 8 weeks of dietary administration, clofazimine massively redistributed from adipose tissue to liver and spleen. During this time, clofazimine concentration in fat and serum significantly decreased, while the mass of clofazimine in spleen and liver increased by >10-fold. These changes were paralleled by the accumulation of clofazimine in the resident macrophages of the lymphatic organs, with as much as 90% of the clofazimine mass in spleen sequestered in intracellular crystal-like drug inclusions (CLDIs). The amount of clofazimine associated with CLDIs of liver and spleen macrophages disproportionately increased and ultimately accounted for a major fraction of the total clofazimine in the host. After treatment was discontinued, clofazimine was retained in spleen while its concentrations decreased in blood and other organs. Immunologically, clofazimine bioaccumulation induced a local, monocyte-specific upregulation of various chemokines and receptors. However, interleukin-1 receptor antagonist was also upregulated, and the acute-phase response pathways and oxidant capacity decreased or remained unchanged, marking a concomitant activation of an anti-inflammatory response. These experiments indicate an inducible, immune system-dependent, xenobiotic sequestration response affecting the atypical pharmacokinetics of a small molecule chemotherapeutic agent.
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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.