ArticleClinical pharmacology and therapeutics2021
Metamizole is a Moderate Cytochrome P450 Inducer Via the Constitutive Androstane Receptor and a Weak Inhibitor of CYP1A2.
Article in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Collecting Metabolite Pharmacokinetics in Drug-Drug Interaction Studies: A Review of Industry Practices and Data Utilization.Clinical pharmacokinetics · 2026Pooled it
- Cytochrome P450 1A2 is the most important enzyme for hepatic metabolism of the metamizole metabolite 4-methylaminoantipyrine.British journal of clinical pharmacology · 2022Trial
- REAMINAS-A Retrospective Study Evaluating the Completeness of the Emergency Department's Admission Medication and Its Influence on Discharge Medication.Journal of clinical medicine · 2026Article
- Article
- Cannabinoid Effects of Metamizol/Dipyrone: A Possible Second Life in Pediatric Anesthesia for a Vintage Drug.Biomedicines · 2026Review
- Metamizole: Indications and Risks.Deutsches Arzteblatt international · 2026Review
- The effect of scheduled metamizole on opioid consumption after cardiac surgery.Frontiers in pharmacology · 2026Article
- Metamizole induces voriconazole metabolism and results in subtherapeutic voriconazole concentrations.British journal of clinical pharmacology · 2025Observational
- Comment on: Increased Theophylline Plasma Concentrations in a Patient With COVID-19.The Annals of pharmacotherapy · 2025Article
- Rifampicin-induced challenges in managing endocrine hypertension and primary aldosteronism: a case report and literature review.Frontiers in pharmacology · 2025Article
- Constitutive androstane receptor, liver pathophysiology and chemical contaminants: current evidence and perspectives.Frontiers in endocrinology · 2025Review
- Developing Quality Indicators for the Pharmacological Management of Chronic Non-Cancer Pain in Older Adult Inpatients: A RAND/UCLA Delphi Study.Journal of pain research · 2025Article
- Metabolite Measurement in Index Substrate Drug Interaction Studies: A Review of the Literature and Recent New Drug Application Reviews.Metabolites · 2024Review
- Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy.Journal of personalized medicine · 2023Article
- Clinical-pharmacological drug information center of Hannover Medical School: experiences and analysis from a tertiary care university hospital.Scientific reports · 2022Article
- Pharmacogenetic Analysis of Voriconazole Treatment in Children.Pharmaceutics · 2022Article
- Inflammatory signaling on cytochrome P450-mediated drug metabolism in hepatocytes.Frontiers in pharmacology · 2022Review
- Metamizole as a Rare Cause of Drug-Induced Liver Injury.European journal of case reports in internal medicine · 2022Article
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7 authors at 3 institutions in 1 country.
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Abstract
Metamizole is an analgesic and antipyretic drug used intensively in certain countries. Previous studies have shown that metamizole induces cytochrome (CYP) 2B6 and possibly CYP3A4. So far, it is unknown whether metamizole induces additional CYPs and by which mechanism. Therefore, we assessed the activity of 6 different CYPs in 12 healthy male subjects before and after treatment with 3 g of metamizole per day for 1 week using a phenotyping cocktail approach. In addition, we investigated whether metamizole induces CYPs by an interaction with the constitutive androstane receptor (CAR) or the pregnane X receptor (PXR) in HepaRG cells. In the clinical study, we confirmed a moderate induction of CYP2B6 (decrease in the efavirenz area under the plasma concentration time curve (AUC) by 79%) and 3A4 (decrease in the midazolam AUC by 68%) by metamizole. In addition, metamizole weakly induced CYP2C9 (decrease in the flurbiprofen AUC by 22%) and moderately CYP2C19 (decrease in the omeprazole AUC by 66%) but did not alter CYP2D6 activity. In addition, metamizole weakly inhibited CYP1A2 activity (1.79-fold increase in the caffeine AUC). We confirmed these results in HepaRG cells, where 4-MAA, the principal metabolite of metamizole, induced the mRNA expression of CYP2B6, 2C9, 2C19, and 3A4. In HepaRG cells with a stable knockout of PXR or CAR, we could demonstrate that CYP induction by 4-MAA depends on CAR and not on PXR. In conclusion, metamizole is a broad CYP inducer by an interaction with CAR and an inhibitor of CYP1A2. Regarding the widespread use of metamizole, these findings are of substantial clinical relevance.
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