ArticleBritish journal of clinical pharmacology2017
Autoinhibitory properties of the parent but not of the N-oxide metabolite contribute to infusion rate-dependent voriconazole pharmacokinetics.
Article in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Time Course of the Interaction Between Oral Short-Term Ritonavir Therapy with Three Factor Xa Inhibitors and the Activity of CYP2D6, CYP2C19, and CYP3A4 in Healthy Volunteers.Clinical pharmacokinetics · 2024Trial
- Microdialysis of Voriconazole and its N-Oxide Metabolite: Amalgamating Knowledge of Distribution and Metabolism Processes in Humans.Pharmaceutical research · 2022Trial
- Microdosed Cocktail of Three Oral Factor Xa Inhibitors to Evaluate Drug-Drug Interactions with Potential Perpetrator Drugs.Clinical pharmacokinetics · 2019Trial
- Unravelling Voriconazole's Hepatic Metabolism: A Narrative Review on Factors Impacting Voriconazole-N-Oxide Exposure.Mycoses · 2026Review
- Toward Genotype-Informed Dosing of Voriconazole: Head-to-Head Simulations Across CYP2C19 Phenotypes Using Population Pharmacokinetic Models.Pharmaceutics · 2025Article
- Pharmacogenetics of steady-state metabolism, pharmacokinetics, and adverse effects of voriconazole in healthy participants.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Comment on "Understanding Voriconazole Metabolism: A Middle-Out Physiologically-Based Pharmacokinetic Modelling Framework Integrating In Vitro and Clinical Insights".Clinical pharmacokinetics · 2025Article
- Towards Model-Informed Precision Dosing of Voriconazole: Challenging Published Voriconazole Nonlinear Mixed-Effects Models with Real-World Clinical Data.Clinical pharmacokinetics · 2023Article
- Microdialysis of Drug and Drug Metabolite: a Comprehensive In Vitro Analysis for Voriconazole and Voriconazole N-oxide.Pharmaceutical research · 2022Article
- Towards the Elucidation of the Pharmacokinetics of Voriconazole: A Quantitative Characterization of Its Metabolism.Pharmaceutics · 2022Article
- Inflammation Affects Liver Function and the Metabolism of Voriconazole to Voriconazole-N-Oxide in Adult and Elderly Patients.Frontiers in pharmacology · 2022Article
- Application of Population Pharmacokinetic Analysis to Characterize CYP2C19 Mediated Metabolic Mechanism of Voriconazole and Support Dose Optimization.Frontiers in pharmacology · 2021Article
- Oral Yohimbine as a New Probe Drug to Predict CYP2D6 Activity: Results of a Fixed-Sequence Phase I Trial.Clinical pharmacokinetics · 2020Article
- A Physiologically Based Pharmacokinetic Model of Voriconazole Integrating Time-Dependent Inhibition of CYP3A4, Genetic Polymorphisms of CYP2C19 and Predictions of Drug-Drug Interactions.Clinical pharmacokinetics · 2020Article
- A Personalized CYP2C19 Phenotype-Guided Dosing Regimen of Voriconazole Using a Population Pharmacokinetic Analysis.Journal of clinical medicine · 2019Article
- Rivaroxaban and macitentan can be coadministered without dose adjustment but the combination of rivaroxaban and St John's wort should be avoided.British journal of clinical pharmacology · 2018Article
- Optimal infusion rate in antimicrobial therapy explosion of evidence in the last five years.Infection and drug resistance · 2018Review
- Autoinhibitory properties of the parent but not of the N-oxide metabolite contribute to infusion rate-dependent voriconazole pharmacokinetics.British journal of clinical pharmacology · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe pharmacokinetics of voriconazole show a nonlinear dose-exposure relationship caused by inhibition of its own CYP3A-dependent metabolism. Because the magnitude of autoinhibition also depends on voriconazole concentrations, infusion rate might modulate voriconazole exposure. The impact of four different infusion rates on voriconazole pharmacokinetics was investigated.
methodsTwelve healthy participants received 100 mg voriconazole intravenous over 4 h, 400 mg over 6 h, 4 h, and 2 h in a crossover design. Oral midazolam (3 μg) was given at the end of infusion. Blood and urine samples were collected up to 48 h. Voriconazole and its N-oxide metabolite were quantified using high-performance liquid chromatography coupled to tandem mass spectrometry. Midazolam estimated metabolic clearance (eCLmet) was calculated using a limited sampling strategy. Voriconazole-N-oxide inhibition of cytochrome P450 (CYP) isoforms 2C19 and 3A4 were assessed with the P450-Glo luminescence assay.
resultsArea under the concentration-time curve for 400 mg intravenous voriconazole was 16% (90% confidence interval: 12-20%) lower when administered over 6 h compared to 2 h infusion. Dose-corrected area under the concentration-time curve for 100 mg over 4 h was 34% lower compared to 400 mg over 4 h. Midazolam eCLmet was 516 ml min
conclusionsVoriconazole pharmacokinetics is modulated by infusion rate, an autoinhibitory contribution voriconazole metabolism by CYP3A and 2C19 and to a lesser extent its main N-oxide metabolite for CYP2C19. To avoid reduced exposure, the infusion rate should be 2 h.
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