ArticleAntimicrobial agents and chemotherapy2011
Population pharmacokinetics of fluconazole in critically ill patients receiving continuous venovenous hemodiafiltration: using Monte Carlo simulations to predict doses for specified pharmacodynamic targets.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Anti-infective Medicines Use in Children and Neonates With Pre-existing Kidney Dysfunction: A Systematic Review.Frontiers in pediatrics · 2022Pooled it
- Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive Candidiasis in children supported with extracorporeal membrane oxygenation.Antimicrobial agents and chemotherapy · 2015Trial
- Pharmacokinetics of ertapenem in critically ill patients receiving continuous venovenous hemodialysis or hemodiafiltration.Antimicrobial agents and chemotherapy · 2014Trial
- DALI: Defining Antibiotic Levels in Intensive care unit patients: a multi-centre point of prevalence study to determine whether contemporary antibiotic dosing for critically ill patients is therapeutic.BMC infectious diseases · 2012Trial
- Antimicrobial pharmacokinetics in pediatric patients on kidney replacement therapy: a comprehensive narrative review.Pediatric nephrology (Berlin, Germany) · 2026Review
- Population Pharmacokinetic Modeling of Intravenous Fluconazole to Inform eGFR-Based Dosing: A Simulation Study Demonstrating Superiority over Standard Regimens.Pharmaceutics · 2026Article
- A Pharmacokinetic Analysis of Intravenous Fluconazole in Adult Patients Undergoing Mechanical Circulatory Support Device Implantation.Clinical pharmacokinetics · 2026Article
- A fluconazole population pharmacokinetics study to improve target attainment in critically ill patients.Infection · 2026Article
- Fluconazole Dosing for the Prevention ofPharmaceutics · 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
- Optimizing fluconazole dosing in acute renal failure patients undergoing continuous renal replacement therapy: A population pharmacokinetic/pharmacodynamic study.Frontiers in pharmacology · 2025Article
- Parametric and nonparametric population pharmacokinetic analysis of fluconazole in critically ill patients and dosing simulations forAntimicrobial agents and chemotherapy · 2024Article
- Population pharmacokinetics of fluconazole in critically ill patients receiving extracorporeal membrane oxygenation and continuous renal replacement therapy: an ASAP ECMO study.Antimicrobial agents and chemotherapy · 2024Article
- Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients.Microorganisms · 2021Article
- Current fluconazole treatment regimens result in under-dosing of critically ill adults during early therapy.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021Article
- Pharmacokinetics of meropenem in children with sepsis undergoing extracorporeal life support: A prospective observational study.Journal of clinical pharmacy and therapeutics · 2021Observational
- Optimization of Fluconazole Dosing for the Prevention and Treatment of Invasive Candidiasis Based on the Pharmacokinetics of Fluconazole in Critically Ill Patients.Antimicrobial agents and chemotherapy · 2021Observational
- Model-Optimized Fluconazole Dose Selection for Critically Ill Patients Improves Early Pharmacodynamic Target Attainment without the Need for Therapeutic Drug Monitoring.Antimicrobial agents and chemotherapy · 2021Article
- Suboptimal Dosing of Fluconazole in Critically Ill Patients: Time To Rethink Dosing.Antimicrobial agents and chemotherapy · 2020Observational
- Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fluconazole is a widely used antifungal agent that is extensively reabsorbed in patients with normal renal function. However, its reabsorption can be compromised in patients with acute kidney injury, thereby leading to altered fluconazole clearance and total systemic exposure. Here, we explore the pharmacokinetics of fluconazole in 10 critically ill anuric patients receiving continuous venovenous hemodiafiltration (CVVHDF). We performed Monte Carlo simulations to optimize dosing to appropriate pharmacodynamic endpoints for this population. Pharmacokinetic profiles of initial and steady-state doses of 200 mg intravenous fluconazole twice daily were obtained from plasma and CVVHDF effluent. Nonlinear mixed-effects modeling (NONMEM) was used for data analysis and to perform Monte Carlo simulations. For each dosing regimen, the free drug area under the concentration-time curve (fAUC)/MIC ratio was calculated. The percentage of patients achieving an AUC/MIC ratio greater than 25 was then compared for a range of MIC values. A two-compartment model adequately described the disposition of fluconazole in plasma. The estimate for total fluconazole clearance was 2.67 liters/h and was notably 2.3 times faster than previously reported in healthy volunteers. Of this, fluconazole clearance by the CVVHDF route (CL(CVVHDF)) represented 62% of its total systemic clearance. Furthermore, the predicted efficiency of CL(CVVHDF) decreased to 36.8% when filters were in use >48 h. Monte Carlo simulations demonstrated that a dose of 400 mg twice daily maximizes empirical treatment against fungal organisms with MIC up to 16 mg/liter. This is the first study we are aware of that uses Monte Carlo simulations to inform dosing requirements in patients where tubular reabsorption of fluconazole is probably nonexistent.
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