Evidence map›Paper›PMID 25182655›Full record

ArticleAntimicrobial agents and chemotherapy2014

Impact of hypoalbuminemia on voriconazole pharmacokinetics in critically ill adult patients.

Kim Vanstraelen, Joost Wauters, Ine Vercammen, Henriette de Loor, Johan Maertens, Katrien Lagrou, Pieter Annaert, Isabel Spriet

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Incorporating the metabolic ratio (C-Frontiers in pharmacology · 2026
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  6. Article
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  8. Voriconazole in the treatment of pediatric patients with hematologic malignancies and invasive fungal infections: a real-world study.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Kim VanstraelenClinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven, Leuven, Belgium kim_vanstraelen@hotmail.com.
Joost WautersClinical Department of General Internal Medicine, Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium.
Ine VercammenClinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven, Leuven, Belgium.
Henriette de LoorDepartment of Microbiology and Immunology, Laboratory of Nephrology and Renal Transplantation, University Hospitals Leuven/KU Leuven, Leuven, Belgium.
Johan MaertensClinical Department of Haematology, Acute Leukaemia and Stem Cell Transplantation Unit, University Hospitals Leuven, Leuven, Belgium.
Katrien LagrouClinical Department of Laboratory Medicine, Department of Microbiology and Immunology, University Hospitals Leuven, Leuven, Belgium.
Pieter AnnaertDepartment of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
Isabel SprietClinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven, Leuven, Belgium.
KU Leuven · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Setting the adequate dose for voriconazole is challenging due to its variable pharmacokinetics. We investigated the impact of hypoalbuminemia (<35 g/liter) on voriconazole pharmacokinetics in adult intensive care unit (ICU) patients treated with voriconazole (20 samples in 13 patients) as well as in plasma samples from ICU patients that had been spiked with voriconazole at concentrations of 1.5 mg/liter, 2.9 mg/liter, and 9.0 mg/liter (66 samples from 22 patients). Plasma albumin concentrations ranged from 13.8 to 38.7 g/liter. Total voriconazole concentrations in adult ICU patients treated with voriconazole ranged from 0.5 to 8.7 mg/liter. Unbound and bound voriconazole concentrations were separated using high-throughput equilibrium dialysis followed by liquid chromatography-tandem mass spectrometry (LC-MSMS). Multivariate analysis revealed a positive relationship between voriconazole plasma protein binding and plasma albumin concentrations (P < 0.001), indicating higher unbound voriconazole concentrations with decreasing albumin concentrations. The correlation is more pronounced in the presence of elevated bilirubin concentrations (P = 0.05). We therefore propose to adjust the measured total voriconazole concentrations in patients with abnormal plasma albumin and total serum bilirubin plasma concentrations who show adverse events potentially related to voriconazole via a formula that we developed. Assuming 50% protein binding on average and an upper limit of 5.5 mg/liter for total voriconazole concentrations, the upper limit for unbound voriconazole concentrations is 2.75 mg/liter. Alterations in voriconazole unbound concentrations caused by hypoalbuminemia and/or elevated bilirubin plasma concentrations cannot be countered immediately, due to the adult saturated hepatic metabolism. Consequently, increased unbound voriconazole concentrations can possibly cause adverse events, even when total voriconazole concentrations are within the reference range.

Indexed as

AgedAntifungal AgentsBilirubinBlood ProteinsChromatography, LiquidCritical IllnessFemaleHumansHypoalbuminemiaIntensive Care UnitsInvasive Pulmonary AspergillosisLiver Function TestsMaleMiddle AgedProspective StudiesProtein BindingAntifungal AgentsBilirubinBlood ProteinsSerum AlbuminVoriconazole

Identifiers

PMID25182655
PMCPMC4249353
OpenAlexW2058223872

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.