ArticleClinical pharmacokinetics2023
Population Pharmacokinetics of Total and Unbound Isavuconazole in Critically Ill Patients: Implications for Adaptive Dosing Strategies.
Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04777058 (Pharmacokinetics of Isavuconazole), which is not on this map. Cited by 16 papers.
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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.
Pharmacokinetics of Isavuconazole (Cresemba®) Given as Treatment of Invasive Fungal Infections in Patients in the Intensive Care Unit
Who cites it
16 citing papers in PubMed, 16 citations in OpenAlex.
- Population pharmacokinetics, target attainment and individualized dosing of isavuconazole in critically ill adults receiving extracorporeal membrane oxygenation.JAC-antimicrobial resistance · 2026Article
- Characterization of isavuconazole pharmacokinetics and pharmacodynamics in a real-life cohort.JAC-antimicrobial resistance · 2026Article
- Exploratory model-based optimizing isavuconazole dosing regimens forFrontiers in cellular and infection microbiology · 2026Article
- Therapeutic drug monitoring-guided optimization of isavuconazole dose for ICU patients with refractory pulmonary aspergillosis: case report.Frontiers in medicine · 2026Article
- Toward adaptive therapeutic timing: integration of mechanistic pharmacology and artificial intelligence in precision dosing.Frontiers in pharmacology · 2026Review
- Use of isavuconazole in critically ill patients in intensive care units: a prospective, observational, multicentre, cohort study.JAC-antimicrobial resistance · 2025Article
- Low isavuconazole trough levels in critically ill patients with and without extracorporeal membrane oxygenation.Antimicrobial agents and chemotherapy · 2025Article
- Equivalent concentration of isavuconazole administered via enteral feeding tube compared to IV or oral formulation in patients treated for invasive pulmonary aspergillosis.Intensive care medicine · 2025Article
- Pharmacokinetics of Isavuconazole During Extracorporeal Membrane Oxygenation Support in Critically Ill Patients: A Case Series.Antibiotics (Basel, Switzerland) · 2025Article
- An Overview of Isavuconazole Clinical Use: A Multicentre Analysis of Indications, Exposure and Hepatic Safety.Clinical drug investigation · 2025Article
- Are contemporary antifungal doses sufficient for critically ill patients? Outcomes from an international, multicenter pharmacokinetics study for Screening Antifungal Exposure in Intensive Care Units-the SAFE-ICU study.Intensive care medicine · 2025Article
- Isolate Specific Transcriptome Changes Exerted by Isavuconazole Treatment in Candida auris.Mycopathologia · 2024Article
- Isavuconazole as prophylaxis and therapy for invasive fungal diseases: a real-life observational study.The Journal of antimicrobial chemotherapy · 2024Observational
- Isavuconazole Pharmacokinetics in Critically Ill Patients: Relationship with Clinical Effectiveness and Patient Safety.Antibiotics (Basel, Switzerland) · 2024Article
- Article
- High Variability in Isavuconazole Unbound Fraction in Clinical Practice: A Call to Reconsider Pharmacokinetic/Pharmacodynamic Targets and Breakpoints.Clinical pharmacokinetics · 2023Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesIsavuconazole is a broad-spectrum antifungal agent for the management of invasive fungal disease. Optimised drug exposure is critical for patient outcomes, specifically in the critically ill population. Solid information on isavuconazole pharmacokinetics including protein binding in patients in the intensive care unit is scarce. We aimed to describe the total and unbound isavuconazole pharmacokinetics and subsequently propose a dosage optimisation strategy.
methodsA prospective multi-centre study in adult intensive care unit patients receiving isavuconazole was performed. Blood samples were collected on eight timepoints over one dosing interval between days 3-7 of treatment and optionally on one timepoint after discontinuation. Total and unbound isavuconazole pharmacokinetics were analysed by means of population pharmacokinetic modelling using NONMEM. The final model was used to perform simulations to assess exposure described by the area under the concentration-time curve and propose an adaptive dosing approach.
resultsPopulation pharmacokinetics of total and unbound isavuconazole were best described by an allometrically scaled two-compartment model with a saturable protein-binding model and interindividual variability on clearance and the maximum binding capacity. The median (range) isavuconazole unbound fraction was 1.65% (0.83-3.25%). After standard dosing, only 35.8% of simulated patients reached a total isavuconazole area under the concentration-time curve > 60 mg·h/L at day 14. The proposed adaptive dosing strategy resulted in an increase to 62.3% of patients at adequate steady-state exposure.
conclusionsIn critically ill patients, total isavuconazole exposure is reduced and protein binding is highly variable. We proposed an adaptive dosing approach to enhance early treatment optimisation in this high-risk population. CLINICAL
trial registrationClinicalTrials.gov identifier: NCT04777058.
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