Observational studyCritical care (London, England)2019
Population pharmacokinetics of total and unbound concentrations of intravenous posaconazole in adult critically ill patients.
Observational study in Critical care (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Factors affecting posaconazole plasma concentrations: a meta-analysis and systematic review.Frontiers in pharmacology · 2024Pooled it
- Hypoalbuminemia and Posaconazole Therapeutic Drug Monitoring.Open forum infectious diseases · 2024Trial
- Posaconazole Target Attainment in Critically Ill Children: A 15-Year Single-Center Retrospective Analysis.Clinical and translational science · 2026Article
- Subtherapeutic posaconazole exposure during delayed-release tablet prophylaxis in high-risk patients with haematological malignancies: rationale for routine therapeutic drug monitoring.The Journal of antimicrobial chemotherapy · 2026Observational
- Posaconazole therapeutic drug monitoring in pediatrics: a single-center retrospective study.BMC pediatrics · 2026Article
- Approaches for posaconazole therapeutic drug monitoring and their clinical benefits.European journal of clinical pharmacology · 2024Review
- Real-world Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels.Open forum infectious diseases · 2024Article
- Article
- Hypoalbuminemia and Pharmacokinetics: When the Misunderstanding of a Fundamental Concept Leads to Repeated Errors over Decades.Antibiotics (Basel, Switzerland) · 2023Review
- A Review of Population Pharmacokinetic Models of Posaconazole.Drug design, development and therapy · 2022Review
- Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients.Antimicrobial agents and chemotherapy · 2020Article
- What Are the Current Approaches to Optimising Antimicrobial Dosing in the Intensive Care Unit?Pharmaceutics · 2020Review
- Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological Disorders.Frontiers in pharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe population pharmacokinetics of total and unbound posaconazole following intravenous administration has not yet been described for the critically ill patient population. The aim of this work was, therefore, to describe the total and unbound population pharmacokinetics of intravenous posaconazole in critically ill patients and identify optimal dosing regimens.
methodsThis was a prospective observational population pharmacokinetic study in critically ill adult patients with presumed/confirmed invasive fungal infection. A single dose of 300 mg posaconazole was administered intravenously as an add-on to standard antifungal therapy, and serial plasma samples were collected over 48 h. Total and unbound posaconazole concentrations, measured by chromatographic method, were used to develop a population pharmacokinetic model and perform dosing simulations in R using Pmetrics.
resultsFrom eight patients, 93 pairs of total and unbound concentrations were measured. A two-compartment linear model with capacity-limited plasma protein binding best described the concentration-time data. Albumin and body mass index (BMI) were included as covariates in the final model. Mean (SD) parameter estimates for the volume of the central compartment (V) and the elimination rate constant were 72 (43) L and 42.1 (23.7) h
conclusionsAn important clinical message of this study is that critically ill patients with increased BMI may require larger than approved loading doses of intravenous posaconazole when considering currently recommended dosing targets. Variability in plasma albumin concentration appears unlikely to affect dosing requirements when the assessment is based on unbound concentrations. Where available, therapeutic drug monitoring of unbound concentrations may be useful.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.