Evidence map›Paper›PMID 38532053›Full record

ArticleClinical pharmacokinetics2024

Personalized Antifungal Therapy Through Model-Informed Precision Dosing of Posaconazole.

Anouk M E Jansen, Kim Snijdelaar, Ron J Keizer, Isabel Spriet, Erwin Dreesen, Roger J M Brüggemann, Rob Ter Heine

Open access · hybridAbstract read
In one paragraph

Article in Clinical pharmacokinetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.6field-weighted citation impact, top 19% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
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

7 authors at 2 institutions in 2 countries.

Anouk M E JansenDepartment of Pharmacy, Radboud University Medical Center, Radboud Institute for Medical Innovation, Nijmegen, The Netherlands. anouk.me.jansen@radboudumc.nl.ORCID 0000-0002-4736-6515
Kim SnijdelaarDepartment of Pharmacy, Radboud University Medical Center, Radboud Institute for Medical Innovation, Nijmegen, The Netherlands.
Ron J KeizerInsightRX, San Francisco, CA, USA.
Isabel SprietDepartment of Pharmacy, University Hospitals Leuven, Leuven, Belgium.
Erwin DreesenDepartment of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Roger J M Brüggemann *Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Medical Innovation, Nijmegen, The Netherlands.
Rob Ter Heine *Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Medical Innovation, Nijmegen, The Netherlands.
Radboud University Nijmegen · NLKU Leuven · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivePosaconazole is a pharmacotherapeutic pillar for prophylaxis and treatment of invasive fungal diseases. Dose individualization is of utmost importance as achieving adequate antifungal exposure is associated with improved outcome. This study aimed to select and evaluate a model-informed precision dosing strategy for posaconazole.

methodsAvailable population pharmacokinetic models for posaconazole administered as a solid oral tablet were extracted from the literature and evaluated using data from a previously published prospective study combined with data collected during routine clinical practice. External evaluation and selection of the most accurate and precise model was based on graphical goodness-of-fit and predictive performance. Measures for bias and imprecision included mean percentage error (MPE) and normalized relative root mean squared error (NRMSE), respectively. Subsequently, the best-performing model was evaluated for its a posteriori fit-for-purpose and its suitability in a limited sampling strategy.

resultsSeven posaconazole models were evaluated using 764 posaconazole plasma concentrations from 143 patients. Multiple models showed adequate predictive performance illustrated by acceptable goodness-of-fit and MPE and NRMSE below ± 10% and ± 25%, respectively. In the fit-for-purpose analysis, the selected model showed adequate a posteriori predictive performance. Bias and imprecision were lowest in the presence of two prior measurements. Additionally, this model showed to be useful in a limited sampling strategy as it adequately predicted total posaconazole exposure from one (non-)trough concentration.

conclusionWe validated an MIPD strategy for posaconazole for its fit-for-purpose. Thereby, this study is an important first step towards MIPD-supported posaconazole dosage optimization with the goal to improve antifungal treatment in clinical practice.

Indexed as

Antifungal AgentsModels, BiologicalPrecision MedicineTriazolesAdministration, OralAdultAgedDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedProspective StudiesYoung AdultAntifungal AgentsposaconazoleTriazoles

Identifiers

PMID38532053
PMCPMC11106146
OpenAlexW4393186960

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.