Trial reportEuropean journal of clinical pharmacology2006
Montelukast and zafirlukast do not affect the pharmacokinetics of the CYP2C8 substrate pioglitazone.
Trial report in European journal of clinical pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 38 citations in OpenAlex.
- Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated Metabolism of Montelukast in Humans.Clinical pharmacology and therapeutics · 2018Trial
- Influence of CYP2C8*2 on the pharmacokinetics of pioglitazone in healthy African-American volunteers.Pharmacotherapy · 2013Trial
- Fluconazole but not the CYP3A4 inhibitor, itraconazole, increases zafirlukast plasma concentrations.European journal of clinical pharmacology · 2012Trial
- The CYP2C8 inhibitor gemfibrozil does not affect the pharmacokinetics of zafirlukast.European journal of clinical pharmacology · 2011Trial
- Tolfenamic acid is a potent CYP1A2 inhibitor in vitro but does not interact in vivo: correction for protein binding is needed for data interpretation.European journal of clinical pharmacology · 2007Trial
- Investigation of Thymoquinone as an Inhibitor of CYP2C8/EET Axis.Chembiochem : a European journal of chemical biology · 2026Article
- CYP2C8-Mediated Drug-Drug Interactions and the Factors Influencing the Interaction Magnitude.Drug design, development and therapy · 2025Review
- Article
- Effect of pterostilbene onSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2019Article
- Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid.The Journal of biological chemistry · 2008Article
- Pharmacokinetic interactions with thiazolidinediones.Clinical pharmacokinetics · 2007Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePioglitazone, a thiazolidinedione antidiabetic drug, is metabolised mainly by the cytochrome P450 (CYP) 2C8 enzyme. The leukotriene receptor antagonists montelukast and zafirlukast have potently inhibited CYP2C8 activity and the metabolism of pioglitazone in vitro. Our objective was to determine whether montelukast and zafirlukast increase the plasma concentrations of pioglitazone in humans.
methodsIn a randomised, double-blind crossover study with three phases and a washout period of 3 weeks, 12 healthy volunteers took either 10 mg montelukast once daily and placebo once daily, or 20 mg zafirlukast twice daily, or placebo twice daily, for 6 days. On day 3, they received a single oral dose of 15 mg pioglitazone. The plasma concentrations of pioglitazone and its metabolites M-IV, M-III, M-V and M-XI were measured for 96 h.
resultsThe total area under the plasma concentration-time curve of pioglitazone during the montelukast and zafirlukast phases was 101% (range 71-143%) and 103% (range 78-146%), respectively, of that during the placebo phase. Also, the peak plasma concentration and elimination half-life of pioglitazone remained unaffected by montelukast and zafirlukast. There were no statistically significant differences in the pharmacokinetics of any of the metabolites of pioglitazone between the phases.
conclusionsMontelukast and zafirlukast do not increase the plasma concentrations of pioglitazone, indicating that their inhibitory effect on CYP2C8 is negligible in vivo, despite their strong inhibitory effect on CYP2C8 in vitro. The results highlight the importance of in vivo interaction studies and of the incorporation of relevant pharmacokinetic properties of drugs, including plasma protein binding data, to in vitro-in vivo interaction predictions.
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