ArticleDrug metabolism and disposition: the biological fate of chemicals2015
In Vitro Metabolism of Montelukast by Cytochrome P450s and UDP-Glucuronosyltransferases.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- The efficacy and safety of combining different Chinese patent medicines with conventional Western drugs in the treatment of pediatric allergic rhinitis: network meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Antileukotrienes for the prevention and treatment of chronic lung disease in very preterm newborns: a systematic review.Respiratory research · 2021Pooled it
- Pharmacokinetics and Bioequivalence Evaluation of Two Montelukast Sodium Chewable Tablets in Healthy Chinese Volunteers Under Fasted and Fed Conditions.Drug design, development and therapy · 2021Trial
- Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese Children.Drug design, development and therapy · 2019Trial
- Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated Metabolism of Montelukast in Humans.Clinical pharmacology and therapeutics · 2018Trial
- The Cytochrome P450 2C8*3 Variant (rs11572080) Is Associated with Improved Asthma Symptom Control in Children and Altered Lipid Mediator Production and Inflammatory Response in Human Bronchial Epithelial Cells.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Interplay of UDP-Glucuronosyltransferase and CYP2C8 for CYP2C8 Mediated Drug Oxidation and Its Impact on Drug-Drug Interaction Produced by Standardized CYP2C8 Inhibitors, Clopidogrel and Gemfibrozil.Clinical pharmacokinetics · 2024Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Leukotrienes vs. Montelukast-Activity, Metabolism, and Toxicity Hints for Repurposing.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Pharmacogenomics of Leukotriene Modifiers: A Systematic Review and Meta-Analysis.Journal of personalized medicine · 2022Article
- Pilot Study of Peak Plasma Concentration After High-Dose Oral Montelukast in Children With Acute Asthma Exacerbations.Journal of clinical pharmacology · 2021Observational
- Identification and characterization of the enzymes responsible for the metabolism of the non-steroidal anti-inflammatory drugs, flunixin meglumine and phenylbutazone, in horses.Journal of veterinary pharmacology and therapeutics · 2021Article
- Montelukast Nanocrystals for Transdermal Delivery with Improved Chemical Stability.Pharmaceutics · 2019Article
- Amenamevir: Studies of Potential CYP2C8- and CYP2B6-Mediated Pharmacokinetic Interactions With Montelukast and Bupropion in Healthy Volunteers.Clinical pharmacology in drug development · 2018Article
- Comprehensive Pharmacogenomic Study Reveals an Important Role of UGT1A3 in Montelukast Pharmacokinetics.Clinical pharmacology and therapeutics · 2018Article
- In Vitro Drug-Drug Interaction Potential of Sulfoxide and/or Sulfone Metabolites of Albendazole, Triclabendazole , Aldicarb, Methiocarb, Montelukast and Ziprasidone.Drug metabolism letters · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Montelukast has been recommended as a selective in vitro and in vivo probe of cytochrome P450 (P450) CYP2C8 activity, but its selectivity toward this enzyme remains unclear. We performed detailed characterization of montelukast metabolism in vitro using human liver microsomes (HLMs), expressed P450s, and uridine 5'-diphospho-glucuronosyltransferases (UGTs). Kinetic and inhibition experiments performed at therapeutically relevant concentrations reveal that CYP2C8 and CYP2C9 are the principal enzymes responsible for montelukast 36-hydroxylation to 1,2-diol. CYP3A4 was the main catalyst of montelukast sulfoxidation and stereoselective 21-hydroxylation, and multiple P450s participated in montelukast 25-hydroxylation. We confirmed direct glucuronidation of montelukast to an acyl-glucuronide. We also identified a novel peak that appears consistent with an ether-glucuronide. Kinetic analysis in HLMs and experiments in expressed UGTs indicate that both metabolites were exclusively formed by UGT1A3. Comparison of in vitro intrinsic clearance in HLMs suggest that direct glucuronidation may play a greater role in the overall metabolism of montelukast than does P450-mediated oxidation, but the in vivo contribution of UGT1A3 needs further testing. In conclusion, our in vitro findings provide new insight toward montelukast metabolism. The utility of montelukast as a probe of CYP2C8 activity may be compromised owing to involvement of multiple P450s and UGT1A3 in its metabolism.
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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.