ArticleAntimicrobial agents and chemotherapy2009
Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3A.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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.
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
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Efficacy and safety of isavuconazole for invasive fungal infections: A systematic review and meta-analysis of randomized controlled trials.Medical mycology · 2025Pooled it
- Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Inhaled Voriconazole in Healthy Volunteers and Subjects With Stable Asthma.Pharmacology research & perspectives · 2025Trial
- Voriconazole greatly increases the exposure to oral buprenorphine.European journal of clinical pharmacology · 2018Trial
- Dose-Dependent Bioavailability and CYP3A Inhibition Contribute to Non-Linear Pharmacokinetics of Voriconazole.Clinical pharmacokinetics · 2016Trial
- Inhibition of Cytochrome P450 2B6 Activity by Voriconazole Profiled Using Efavirenz Disposition in Healthy Volunteers.Antimicrobial agents and chemotherapy · 2016Trial
- A semiphysiological population pharmacokinetic model for dynamic inhibition of liver and gut wall cytochrome P450 3A by voriconazole.Clinical pharmacokinetics · 2013Trial
- Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects.Clinical pharmacokinetics · 2013Trial
- Plasma letrozole concentrations in postmenopausal women with breast cancer are associated with CYP2A6 genetic variants, body mass index, and age.Clinical pharmacology and therapeutics · 2011Trial
- Tacrolimus use in adult allogeneic stem cell transplant recipients receiving voriconazole: preemptive dose modification and therapeutic drug monitoring.Bone marrow transplantation · 2010Trial
- Exploring the impacts of flavonoid compounds on escitalopram metabolism: a combined in vitro and in vivo study.Molecular diversity · 2026Article
- Mechanistic insights into voriconazole-exacerbated selpercatinib-induced thrombocytopenia: a pharmacokinetic interaction case report.Frontiers in oncology · 2026Article
- Exploring Long Arm Amide-Linked Side Chains in the Design of Antifungal Azole Inhibitors of Sterol 14α-Demethylase (CYP51).Journal of medicinal chemistry · 2025Article
- Current Updates on Pathogenesis, Systemic Therapy, and Treatment of Invasive Fungal Infections.Current drug targets · 2025Review
- Article
- Pharmacokinetic Model of Drug Interaction of Tacrolimus with Combined Administration of CYP3A4 Inhibitors Voriconazole and Clarithromycin After Bone Marrow Transplantation.European journal of drug metabolism and pharmacokinetics · 2024Article
- Assessment of omeprazole and famotidine effects on the pharmacokinetics of tacrolimus in patients following kidney transplant-randomized controlled trial.Frontiers in pharmacology · 2024Article
- Drug-drug interaction prediction of ziritaxestat using a physiologically based enzyme and transporter pharmacokinetic network interaction model.Clinical and translational science · 2023Article
- Towards Model-Informed Precision Dosing of Voriconazole: Challenging Published Voriconazole Nonlinear Mixed-Effects Models with Real-World Clinical Data.Clinical pharmacokinetics · 2023Article
- Pharmacokinetic interaction of voriconazole and clarithromycin in Pakistani healthy male volunteers: a single dose, randomized, crossover, open-label study.Frontiers in pharmacology · 2023Article
- Dual Inhibition of CYP3A4 by Voriconazole and Clarithromycin Influences Tacrolimus Pharmacokinetics: Case Series Study.European journal of drug metabolism and pharmacokinetics · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Voriconazole is an effective antifungal drug, but adverse drug-drug interactions associated with its use are of major clinical concern. To identify the mechanisms of these interactions, we tested the inhibitory potency of voriconazole with eight human cytochrome P450 (CYP) enzymes. Isoform-specific probes were incubated with human liver microsomes (HLMs) (or expressed CYPs) and cofactors in the absence and the presence of voriconazole. Preincubation experiments were performed to test mechanism-based inactivation. In pilot experiments, voriconazole showed inhibition of CYP2B6, CYP2C9, CYP2C19, and CYP3A (half-maximal [50%] inhibitory concentrations, <6 microM); its effect on CYP1A2, CYP2A6, CYP2C8, and CYP2D6 was marginal (<25% inhibition at 100 microM voriconazole). Further detailed experiments with HLMs showed that voriconazole is a potent competitive inhibitor of CYP2B6 (K(i) < 0.5), CYP2C9 (K(i) = 2.79 microM), and CYP2C19 (K(i) = 5.1 microM). The inhibition of CYP3A by voriconazole was explained by noncompetitive (K(i) = 2.97 microM) and competitive (K(i) = 0.66 microM) modes of inhibition. Prediction of the in vivo interaction of voriconazole from these in vitro data suggests that voriconazole would substantially increase the exposure of drugs metabolized by CYP2B6, CYP2C9, CYP2C19, and CYP3A. Clinicians should be aware of these interactions and monitor patients for adverse effects or failure of therapy.
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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.