ArticleClinical pharmacokinetics2021
Evaluation of Voriconazole CYP2C19 Phenotype-Guided Dose Adjustments by Physiologically Based Pharmacokinetic Modeling.
Article in Clinical pharmacokinetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Pre-emptiveFrontiers in pharmacology · 2026Trial
- The Predictive Value of Initial Trough Concentration of Voriconazole and Procalcitonin in Hepatotoxic Adverse Events.Drug design, development and therapy · 2025Article
- Voriconazole: a review of adjustment programs guided by therapeutic drug monitoring.Frontiers in pharmacology · 2024Review
- Factors affecting voriconazole concentration to dose ratio changes according to route of administration.European journal of hospital pharmacy : science and practice · 2023Article
- Impact of CYP2C:TG Haplotype on CYP2C19 Substrates Clearance In Vivo, Protein Content, and In Vitro Activity.Clinical pharmacology and therapeutics · 2023Article
- Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections.Pharmaceutics · 2023Review
- Impact of polymorphisms inFrontiers in pharmacology · 2023Article
- The impact of gene polymorphism and hepatic insufficiency on voriconazole dose adjustment in invasive fungal infection individuals.Frontiers in genetics · 2023Review
- Therapeutic drug monitoring and safety evaluation of voriconazole in the treatment of pulmonary fungal diseases.Therapeutic advances in drug safety · 2022Article
- Modeling Approach to Predict the Impact of Inflammation on the Pharmacokinetics of CYP2C19 and CYP3A4 Substrates.Pharmaceutical research · 2021Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesControversy exists regarding dose adjustment in patients treated with voriconazole due to the severity of the infections for which it is prescribed. The Dutch Pharmacogenetics Working Group (DPWG) recommends a 50% dose increase or decrease for cytochrome P450 (CYP) 2C19 ultrarapid (UM) or poor (PM) metabolizers, respectively. In contrast, for the previous phenotypes, the Clinical Pharmacogenetics Implementation Consortium (CPIC) voriconazole guideline only recommends a change of treatment. Based on observed data from single-dose bioequivalence studies and steady-state observed concentrations, we aimed to investigate voriconazole dose adjustments by means of physiologically based pharmacokinetic (PBPK) modeling.
methodsPBPK modeling was used to optimize voriconazole single-dose models for each CYP2C19 phenotype, which were extrapolated to steady state and evaluated for concordance with the therapeutic range of voriconazole. Based on optimized models, dose adjustments were evaluated for better adjustment to the therapeutic range.
resultsOur models suggest that the standard dose may only be appropriate for normal metabolizers (NM), although they would benefit from a 50-100% loading dose increase. Intermediate metabolizers (IMs) and PMs required a daily dose reduction of 50 and 75%, respectively. Rapid metabolizers (RMs) and UMs required a daily dose increase of 100% and 300%, respectively.
conclusionThe prescription of voriconazole in clinical practice should be personalized according to the CYP2C19 phenotype, followed by therapeutic drug monitoring of plasma concentrations to guide dose adjustment.
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