Evidence map›Paper›PMID 39437712›Full record

ArticleTherapeutic drug monitoring2025

Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Voriconazole for Predicting the Clinical Outcomes of Adult Patients With Invasive Aspergillosis.

Monchai Duangpraphat, Richard C Wilson, Timothy M Rawson, Wichai Santimaleeworagun, Worapong Nasomsong, Alison H Holmes, Vasin Vasikasin

Abstract read
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Article in Therapeutic drug monitoring, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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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

1 citing paper in PubMed.

  1. Review
4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Monchai DuangpraphatDepartment of Internal Medicine, Phramongkutklao Hospital and College of Medicine, Ratchadhevi, Bangkok, Thailand.
Richard C WilsonCentre for Antimicrobial Optimisation, Imperial College London, United Kingdom.
Timothy M RawsonCentre for Antimicrobial Optimisation, Imperial College London, United Kingdom.
Wichai SantimaleeworagunDepartment of Internal Medicine, Phramongkutklao Hospital and College of Medicine, Ratchadhevi, Bangkok, Thailand.
Worapong NasomsongDepartment of Internal Medicine, Phramongkutklao Hospital and College of Medicine, Ratchadhevi, Bangkok, Thailand.
Alison H HolmesCentre for Antimicrobial Optimisation, Imperial College London, United Kingdom.
Vasin VasikasinDepartment of Internal Medicine, Phramongkutklao Hospital and College of Medicine, Ratchadhevi, Bangkok, Thailand.ORCID 0000-0002-1761-0978

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundVoriconazole is the first-line therapy for invasive aspergillosis (IA). To determine the minimum inhibitory concentration of Aspergillus, a voriconazole pharmacokinetic-pharmacodynamic (PK-PD) model linked to galactomannan response was developed and evaluated, and its clinical correlation for IA treatment was elucidated.

methodsAdult patients with probable or definite IA and at least one serum voriconazole measurement were included. A two-compartment voriconazole PK model was linked to a previously described PD model of galactomannan response. PK and PD parameters were estimated using a nonparametric adaptive grid technique. The relationship between the ratio of voriconazole exposure that induced half-maximum galactomannan response (EC50) and the observed terminal galactomannan concentration was evaluated. The factors associated with the PK-PD parameters and mortality were also determined.

resultsBetween January 2013 and December 2022, 41 patients were prescribed voriconazole for IA. The 30-day mortality rate was 17%. A high correlation was found for the observed-predicted Bayesian posterior estimates of voriconazole and galactomannan levels. Moreover, a nonlinear relationship was identified between AUC:EC50 and terminal galactomannan. The factors associated with higher AUC:EC50 were intravenous administration and intubation. In the survival analysis, higher EC50 tended to be associated with mortality, higher AUC was significantly associated with increased mortality, and higher AUC:EC50 tended to be associated with higher mortality. After adjusting for the intravenous route, higher AUC and AUC:EC50 were not associated with mortality.

conclusionsIndividual EC50 estimation can provide insights into in vivo host and organism responses. Elevated EC50 showed comparable and unfavorable trends to higher minimum inhibitory concentration. Thus, determining EC50 might help guide individualized target serum voriconazole levels.

Indexed as

Antifungal AgentsAspergillosisVoriconazoleAdultAgedArea Under CurveBayes TheoremFemaleGalactoseHumansMaleMannansMicrobial Sensitivity TestsMiddle AgedModels, BiologicalTreatment OutcomeAntifungal AgentsgalactomannanGalactoseMannansVoriconazolegalactomannaninvasive aspergillosispharmacokinetic–pharmacodynamic modelvoriconazole

Identifiers

PMID39437712
PMCPMC12061369

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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.