ArticleToxicology and applied pharmacology2008
Metabolism of the anti-tuberculosis drug ethionamide by mouse and human FMO1, FMO2 and FMO3 and mouse and human lung microsomes.
Article in Toxicology and applied pharmacology, 2008. 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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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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- A resource for integrated genomic analysis of the human liver.Scientific reports · 2022Pooled it
- snRNA-seq identifies Fmo2npj metabolic health and disease · 2026Article
- Alpibectir-Ethionamide combination (AlpE) for the treatment of tuberculosis.Nature communications · 2026Article
- FMO2 Promotes Angiogenesis via Regulation of N-Acetylornithine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- A scoping review about smoking, smoking cessation and their effects on anti-tuberculosis agents: insights into drug metabolisms, safety, and effectiveness.Frontiers in pharmacology · 2025Review
- Formation of potentially toxic metabolites of drugs in reactions catalyzed by human drug-metabolizing enzymes.Archives of toxicology · 2024Review
- Genetic structure and selective sweeps in Kirghiz sheep using SNP50K bead chip.Frontiers in genetics · 2024Article
- Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions.Archives of toxicology · 2022Review
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- New insights into ethionamide metabolism: influence of oxidized methionine on its degradation path.RSC medicinal chemistry · 2020Article
- Human Enzymes for Organic Synthesis.Angewandte Chemie (International ed. in English) · 2018Review
- Pharmacokinetics and Drug-Drug Interactions of Lopinavir-Ritonavir Administered with First- and Second-Line Antituberculosis Drugs in HIV-Infected Children Treated for Multidrug-Resistant Tuberculosis.Antimicrobial agents and chemotherapy · 2018Observational
- Article
- Human FMO2-based microbial whole-cell catalysts for drug metabolite synthesis.Microbial cell factories · 2015Article
- Flavin-containing monooxygenase S-oxygenation of a series of thioureas and thiones.Toxicology and applied pharmacology · 2014Article
- Mammalian flavin-containing monooxygenase (FMO) as a source of hydrogen peroxide.Biochemical pharmacology · 2014Article
- Metabolism and pharmacokinetics of the anti-tuberculosis drug ethionamide in a flavin-containing monooxygenase null mouse.Pharmaceuticals (Basel, Switzerland) · 2012Article
- Pharmacokinetics of ethionamide in children.Antimicrobial agents and chemotherapy · 2011Article
- Flavin-containing monooxygenase-3: induction by 3-methylcholanthrene and complex regulation by xenobiotic chemicals in hepatoma cells and mouse liver.Toxicology and applied pharmacology · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tuberculosis (TB) results from infection with Mycobacterium tuberculosis and remains endemic throughout the world with one-third of the world's population infected. The prevalence of multi-drug resistant strains necessitates the use of more toxic second-line drugs such as ethionamide (ETA), a pro-drug requiring bioactivation to exert toxicity. M. tuberculosis possesses a flavin monooxygenase (EtaA) that oxygenates ETA first to the sulfoxide and then to 2-ethyl-4-amidopyridine, presumably through a second oxygenation involving sulfinic acid. ETA is also a substrate for mammalian flavin-containing monooxygenases (FMOs). We examined activity of expressed human and mouse FMOs toward ETA, as well as liver and lung microsomes. All FMOs converted ETA to the S-oxide (ETASO), the first step in bioactivation. Compared to M. tuberculosis, the second S-oxygenation to the sulfinic acid is slow. Mouse liver and lung microsomes, as well as human lung microsomes from an individual expressing active FMO, oxygenated ETA in the same manner as expressed FMOs, confirming this reaction functions in the major target organs for therapeutics (lung) and toxicity (liver). Inhibition by thiourea, and lack of inhibition by SKF-525A, confirm ETASO formation is primarily via FMO, particularly in lung. ETASO production was attenuated in a concentration-dependent manner by glutathione. FMO3 in human liver may contribute to the toxicity and/or affect efficacy of ETA administration. Additionally, there may be therapeutic implications of efficacy and toxicity in human lung based on the FMO2 genetic polymorphism, though further studies are needed to confirm that suggestion.
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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.