Trial reportEuropean journal of clinical pharmacology2006
The CYP2C8 inhibitor gemfibrozil does not increase the plasma concentrations of zopiclone.
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 10 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.
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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.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Model-based meta-analysis of the effects of non-selective and α1-selective GABAA receptor agonists in healthy volunteers.European journal of clinical pharmacology · 2015Pooled it
- Clozapine Drug-Drug Interactions and Individualized Dosing in Bipolar Disorder: A Model-Informed Precision Dosing Approach.Drug design, development and therapy · 2025Article
- Population pharmacokinetics modelling to predict DDI from zopiclone on clozapine in schizophrenia patients.Frontiers in psychiatry · 2025Article
- CYP2C9 and 3A4 play opposing roles in bioactivation and detoxification of diphenylamine NSAIDs.Biochemical pharmacology · 2021Article
- Meloxicam methyl group determines enzyme specificity for thiazole bioactivation compared to sudoxicam.Toxicology letters · 2021Article
- CYP2C19 and 3A4 Dominate Metabolic Clearance and Bioactivation of Terbinafine Based on Computational and Experimental Approaches.Chemical research in toxicology · 2019Article
- Risk of falling and hypnotic drugs: retrospective study of inpatients.Drugs in R&D · 2013Article
- The Useage of Opioids and their Adverse Effects in Gastrointestinal Practice: A Review.Middle East journal of digestive diseases · 2013Review
- Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.Pharmacogenomics · 2009Article
- Multiple inhibition mechanisms and prediction of drug-drug interactions: status of metabolism and transporter models as exemplified by gemfibrozil-drug interactions.Pharmaceutical research · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveZopiclone is a short acting hypnotic, which is metabolised by cytochrome P450 (CYP) 3A4 and 2C8 in vitro. We studied the possible effect of gemfibrozil, an inhibitor of CYP2C8, on the pharmacokinetics and pharmacodynamics of zopiclone.
methodsIn a randomised 2-phase crossover study, 10 healthy volunteers took 600 mg gemfibrozil or placebo orally twice daily for 3 days. On day 3, each ingested a 7.5 mg dose of zopiclone. Plasma concentrations and urinary excretion of zopiclone and its two primary metabolites, plasma gemfibrozil, and psychomotor performance were measured. The effects of CYP2C8, CYP2C9 and CYP3A4 inhibitors on the depletion of zopiclone (500 nM) were studied in vitro in human liver microsomes.
resultsThe pharmacokinetic variables of the parent zopiclone were not significantly affected by gemfibrozil. However, gemfibrozil raised the mean peak plasma concentration (C(max)) of N-oxide-zopiclone (1.6-fold; P<0.001) and that of N-desmethyl-zopiclone (1.2-fold; P<0.001). The mean area under the plasma concentration-time curve (AUC(0)-infinity) values of N-oxide-zopiclone and N-desmethyl-zopiclone were raised 2-fold (P<0.001) and 1.2-fold (P<0.01), respectively. The renal clearance of N-oxide-zopiclone was reduced by 48% by gemfibrozil (P<0.001). The pharmacodynamic effects of zopiclone, measured using psychometric tests, were not affected by gemfibrozil. In vitro, ketoconazole (1 microM) and itraconazole (8 microM) decreased the elimination rate of zopiclone enantiomers by about 65-95%, while montelukast (16 microM), gemfibrozil (200 microM) and sulfaphenazole (10 microM) had no appreciable effect.
conclusionsGemfibrozil does not increase the plasma concentrations of the parent zopiclone. Accordingly, CYP2C8 does not significantly metabolise zopiclone in vivo. However, as gemfibrozil raises the concentrations of two potentially active metabolites of zopiclone, slightly enhanced effects of zopiclone by gemfibrozil can not be excluded.
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