Trial reportEuropean journal of clinical pharmacology2007
Voriconazole and fluconazole increase the exposure to oral diazepam.
Trial report in European journal of clinical pharmacology, 2007. 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.
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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 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
- Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction.European journal of clinical pharmacology · 2016Trial
- Fluconazole but not the CYP3A4 inhibitor, itraconazole, increases zafirlukast plasma concentrations.European journal of clinical pharmacology · 2012Trial
- Effects of the moderate CYP3A4 inhibitor, fluconazole, on the pharmacokinetics of fesoterodine in healthy subjects.British journal of clinical pharmacology · 2011Trial
- Effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam.British journal of clinical pharmacology · 2010Trial
- Voriconazole drastically increases exposure to oral oxycodone.European journal of clinical pharmacology · 2009Trial
- A Drug-Drug Interaction of Ainuovirine with Fluconazole in Healthy Adults and Dose Optimization Informed by Pharmacokinetics Modelling.Drug design, development and therapy · 2026Article
- Interaction and potential mechanisms between atorvastatin and voriconazole, agents used to treat dyslipidemia and fungal infections.Frontiers in pharmacology · 2023Article
- Development of a simple and sensitive HPLC-MS/MS method for determination of diazepam in human plasma and its application to a bioequivalence study.Translational and clinical pharmacology · 2017Article
- Respiratory depression related to multiple drug-drug interactions precipitated by a fluconazole loading dose in a patient treated with oxycodone.European journal of clinical pharmacology · 2017Article
- A Model for Predicting the Interindividual Variability of Drug-Drug Interactions.The AAPS journal · 2017Article
- Impact of genetic polymorphism on drug-drug interactions mediated by cytochromes: a general approach.The AAPS journal · 2013Article
- In vivo quantitative prediction of the effect of gene polymorphisms and drug interactions on drug exposure for CYP2C19 substrates.The AAPS journal · 2013Article
- Azole interactions with multidrug therapy in pediatric oncology.European journal of clinical pharmacology · 2013Review
- Importance of multi-p450 inhibition in drug-drug interactions: evaluation of incidence, inhibition magnitude, and prediction from in vitro data.Chemical research in toxicology · 2012Review
- Mycoses in the elderly.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2010Review
- Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3A.Antimicrobial agents and chemotherapy · 2009Article
- What is the true risk of a pharmacokinetic drug-drug interaction?European journal of clinical pharmacology · 2007Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveWe assessed the effect of voriconazole and fluconazole on the pharmacokinetics and pharmacodynamics of diazepam.
methodsTwelve healthy volunteers took 5 mg of oral diazepam in a randomised order on three study sessions: without pretreatment, after oral voriconazole 400 mg twice daily on the first day and 200 mg twice daily on the second day, or after oral fluconazole 400 mg on the first day and 200 mg on the second day. Plasma concentrations of diazepam and N-desmethyldiazepam were determined for up to 48 h. Pharmacodynamic variables were measured for 12 h.
resultsIn the voriconazole phase, the area under the plasma concentration time curve (AUC 0-infinity) of diazepam was increased (geometric mean ratio) 2.2-fold (p < 0.05; 90% confidence interval [CI] 1.56 to 2.82). This was associated with the prolongation of the mean elimination half-life (t(1/2)) from 31 h to 61 h (p < 0.01) after voriconazole. In the fluconazole phase, the AUC 0-infinity of diazepam was increased 2.5-fold (p < 0.01; 90% CI 1.94 to 3.40), and the t(1/2) was prolonged from 31 h to 73 h (p < 0.001). The peak plasma concentration of diazepam was practically unchanged by voriconazole and fluconazole. The pharmacodynamics of diazepam were changed only modestly.
conclusionBoth voriconazole and fluconazole considerably increase the exposure to diazepam. Recurrent administration of diazepam increases the risk of clinically significant interactions during voriconazole or fluconazole treatment, because the elimination of diazepam is impaired significantly.
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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.