Trial reportClinical pharmacokinetics2014
A physiologically based pharmacokinetic model for voriconazole disposition predicts intestinal first-pass metabolism in children.
Trial report in Clinical pharmacokinetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- Optimization strategies for voriconazole dosing in pediatric populations: integrating therapeutic indications and age-stratified pharmacokinetics.Antimicrobial agents and chemotherapy · 2026Article
- Advancements in Virtual Bioequivalence: A Systematic Review of Computational Methods and Regulatory Perspectives in the Pharmaceutical Industry.Pharmaceutics · 2024Review
- Voriconazole therapeutic drug monitoring including analysis of CYP2C19 phenotype in immunocompromised pediatric patients with invasive fungal infections.European journal of clinical pharmacology · 2024Article
- Challenges in the Treatment of Invasive Aspergillosis in Immunocompromised Children.Antimicrobial agents and chemotherapy · 2022Review
- Use of modeling and simulation to predict the influence of triazole antifungal agents on the pharmacokinetics of zanubrutinib and acalabrutinib.Frontiers in pharmacology · 2022Article
- Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies.Pharmaceutics · 2021Review
- Clinical Pharmacokinetics of Triazoles in Pediatric Patients.Clinical pharmacokinetics · 2021Review
- Physiologically Based Pharmacokinetic Models Are Effective Support for Pediatric Drug Development.AAPS PharmSciTech · 2021Review
- Evaluation of Voriconazole CYP2C19 Phenotype-Guided Dose Adjustments by Physiologically Based Pharmacokinetic Modeling.Clinical pharmacokinetics · 2021Article
- Application of a Physiologically Based Pharmacokinetic Model to Characterize Time-dependent Metabolism of Voriconazole in Children and Support Dose Optimization.Frontiers in pharmacology · 2021Article
- 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
- Effect of proton pump inhibitors on voriconazole concentrations in Chinese patients with malignant hematological diseases.European journal of clinical pharmacology · 2020Article
- Administration and Dosing of Systemic Antifungal Agents in Pediatric Patients.Paediatric drugs · 2020Review
- Quantitative Systems Pharmacology and Physiologically-Based Pharmacokinetic Modeling With mrgsolve: A Hands-On Tutorial.CPT: pharmacometrics & systems pharmacology · 2019Article
- Physiologically Based Pharmacokinetic Models for Adults and Children Reveal a Role of Intracellular Tubulin Binding in Vincristine Disposition.CPT: pharmacometrics & systems pharmacology · 2019Article
- Frequency of the CYP2C19*17 polymorphism in a Chilean population and its effect on voriconazole plasma concentration in immunocompromised children.Scientific reports · 2019Article
- Voriconazole: A Review of Population Pharmacokinetic Analyses.Clinical pharmacokinetics · 2019Review
- Pediatric Dose Selection and Utility of PBPK in Determining Dose.The AAPS journal · 2018Review
- Cytochrome P450 and flavin-containing monooxygenase families: age-dependent differences in expression and functional activity.Pediatric research · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThe effect of ontogeny in drug-metabolizing enzymes on pediatric pharmacokinetics is poorly predicted. Voriconazole, a potent antifungal, is cleared predominantly via oxidative metabolism and exhibits vastly different pharmacokinetics between adults and children. A physiologically based pharmacokinetic (PBPK) model was developed integrating hepatic in vitro metabolism data with physiologic parameters to predict pharmacokinetic parameters of voriconazole in adult and pediatric populations.
methodsAdult and pediatric PBPK models integrated voriconazole physicochemical properties with hepatic in vitro data into the models. Simulated populations contained 100 patients (10 trials with 10 patients each). Trial design and dosing was based on published clinical trials. Simulations yielded pharmacokinetic parameters that were compared against published values and visual predictive checks were employed to validate models.
resultsAll adult models and the pediatric intravenous model predicted pharmacokinetic parameters that corresponded with observed values within a 20% prediction error, whereas the pediatric oral model predicted an oral bioavailability twofold higher than observed ranges. After incorporating intestinal first-pass metabolism into the model, the prediction of oral bioavailability improved substantially, suggesting that voriconazole is subject to intestinal first-pass metabolism in children, but not in adults.
conclusionsThe PBPK approach used in this study suggests a mechanistic reason for differences in bioavailability between adults and children. If verified, this would be the first example of differential first-pass metabolism in children and adults.
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