Trial reportBritish journal of clinical pharmacology2015
Metabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1.
Trial report in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 29 citations in OpenAlex.
- Bioequivalence study of two formulations of flupirtine maleate capsules in healthy male Chinese volunteers under fasting and fed conditions.Drug design, development and therapy · 2017Trial
- From Retigabine to Azetukalner: Reviving Voltage-Gated Potassium Channels for Epilepsy Therapy.Archiv der Pharmazie · 2026Review
- Discovery of Functionalized 1Journal of medicinal chemistry · 2025Article
- Carba Analogues of Flupirtine and Retigabine with Improved Oxidation Resistance and Reduced Risk of Quinoid Metabolite Formation.ChemMedChem · 2022Article
- Modifications of the Triaminoaryl Metabophore of Flupirtine and Retigabine Aimed at Avoiding Quinone Diimine Formation.ACS omega · 2022Article
- Alternative Targets for Modulators of Mitochondrial Potassium Channels.Molecules (Basel, Switzerland) · 2022Review
- PXR-mediated idiosyncratic drug-induced liver injury: mechanistic insights and targeting approaches.Expert opinion on drug metabolism & toxicology · 2020Review
- Flupirtine Analogues: Explorative Synthesis and Influence of Chemical Structure on KChemistryOpen · 2019Article
- Randomized controlled trial about pain medication flupirtine ignores recent pharmacovigilance warnings.Journal of pain research · 2018Article
- Discovery of Aromatic Carbamates that Confer Neuroprotective Activity by Enhancing Autophagy and Inducing the Anti-Apoptotic Protein B-Cell Lymphoma 2 (Bcl-2).Journal of medicinal chemistry · 2017Article
- Anticonvulsant effect of flupirtine in an animal model of neonatal hypoxic-ischemic encephalopathy.Neuropharmacology · 2017Article
- Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery.PloS one · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe rare association of flupirtine with liver injury is most likely caused by reactive quinone diimines and their oxidative formation may be influenced by the activities of N-acetyltransferases (NAT) that conjugate the less toxic metabolite D13223, and by glucuronosyltransferases (UGT) and glutathione S-transferases (GST) that generate stable terminal glucuronides and mercapturic acid derivatives, respectively. The influence of genetic polymorphisms of NAT2, UGT1A1 and GSTP1 on generation of the terminal mercapturic acid derivatives and analgesic effects was evaluated to identify potential genetic risk factors for hepatotoxicity of flupirtine.
methodsMetabolic disposition of flupirtine was measured after intravenous administration (100 mg), after swallowing an immediate-release (IR) tablet (100 mg) and after repeated administration of modified release (MR) tablets (400 mg once daily 8 days) in 36 selected healthy subjects. Analgesic effects were measured using pain models (delayed onset of muscle soreness, electric pain).
resultsFlupirtine IR was rapidly but incompletely absorbed (∼ 72%). Repeated administration of flupirtine MR showed lower bioavailability (∼ 60%). Approximately 12% of bioavailable flupirtine IR and 8% of bioavailable flupiritine MR was eliminated as mercapturic acid derivatives into the urine independent of the UGT1A1, NAT2 and GSTP1 genotype. Carriers of variant GSTP1 alleles showed lower bioavailability but increased intestinal secretion of flupirtine and increased efficiency in experimental pain. Flupirtine was not a substrate for ABCB1 and ABCC2.
conclusionsFormation of mercapturic acid derivatives is a major elimination route for flupirtine in man. However, the theoretically toxic pathway is not influenced by the frequent polymorphisms of UGT1A1, NAT2 and GSTP1.
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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.