Evidence map›Paper›PMID 37179512›Full record

ArticleClinical pharmacokinetics2023

Population Pharmacokinetics of Posaconazole in Immune-Compromised Children and Assessment of Target Attainment in Invasive Fungal Disease.

Sean McCann, Jaydeep Sinha, William S Wilson, Cameron J McKinzie, Lauren M Garner, Daniel Gonzalez

Open access · hybridAbstract read
In one paragraph

Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. How I Treat: Chronic granulomatous disease.Journal of human immunity · 2026
    Review
  3. Article
  4. Article
  5. Review
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

6 authors at 1 institution in 1 country.

Sean McCannDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, 301 Pharmacy Lane, Campus Box #7569, Chapel Hill, NC, 27599-7569, USA.ORCID http://orcid.org/0000-0003-2723-5398
Jaydeep SinhaDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, 301 Pharmacy Lane, Campus Box #7569, Chapel Hill, NC, 27599-7569, USA.ORCID http://orcid.org/0000-0002-2110-3370
William S WilsonDepartment of Pharmacy, University of North Carolina Medical Center, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-5837-066X
Cameron J McKinzieDepartment of Pharmacy, University of North Carolina Medical Center, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-4920-8067
Lauren M GarnerDepartment of Pharmacy, University of North Carolina Medical Center, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-1675-941X
Daniel GonzalezDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, 301 Pharmacy Lane, Campus Box #7569, Chapel Hill, NC, 27599-7569, USA. daniel.gonzalez@unc.edu.ORCID http://orcid.org/0000-0001-5522-5686
University of North Carolina at Chapel Hill · US

Funding

Application of Physiologically-Based Pharmacokinetic Modeling to Characterize Drug-Drug Interactions in InfantsR01HD102949 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Daniel Gonzalez · 2021 to 2026
$3.0M
Physiologically-Based Pharmacokinetic Modeling to Guide Drug Dosing in Children with ObesityR01HD096435 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DUMOND, JULIE BRUMER · 2018 to 2022
$2.0M
NICHD NIH HHS R01 HD096435NICHD NIH HHS R01 HD102949
6 · The paper itself

Abstract

BACKGROUND AND

objectivePosaconazole (PSZ) is a triazole antifungal for the management of invasive fungal disease (IFD) in adults and children. Although PSZ is available as an intravenous (IV) solution, oral suspension (OS) and delayed-release tablets (DRTs), OS is the preferred formulation for pediatric use because of potential safety concerns associated with an excipient in the IV formulation and difficulty in swallowing intact tablets by children. However, poor biopharmaceutical characteristics of the OS formulation leads to an unpredictable dose-exposure profile of PSZ in children, potentially risking therapeutic failure. The goal of this study was to characterize the population pharmacokinetics (PK) of PSZ in immunocompromised children and assess therapeutic target attainment.

methodsSerum concentrations of PSZ were collected retrospectively from records of hospitalized patients. A population PK analysis was performed in a nonlinear mixed-effects modeling framework with NONMEM (v7.4). The PK parameters were scaled to body weight, then potential covariate effects were assessed. The final PK model was used to evaluate recommended dosing schemes through simulation of target attainment (as a percentage of the population having steady-state trough concentrations above the recommended target) using Simulx (v2021R1).

resultsRepeated measurement data of 202 serum concentrations of total PSZ were acquired from 47 immunocompromised patients between 1 and 21 years of age receiving PSZ either intravenously or orally, or both. A one-compartment PK model with first-order absorption and linear elimination best fit the data. The estimated absolute bioavailability (95% confidence interval) for suspension (F

conclusionsThe results of this study revealed that both fixed and weight-based adaptive dosing schemes can be appropriate for target attainment across all PSZ formulations, including suspension. Additionally, covariate analysis suggests that concomitant proton pump inhibitors should be contraindicated during PSZ suspension dosing.

Indexed as

Invasive Fungal InfectionsAdministration, OralAdultAntifungal AgentsChildHumansRetrospective StudiesSuspensionsTabletsTriazolesAntifungal AgentsposaconazoleSuspensionsTabletsTriazoles

Identifiers

PMID37179512
PMCPMC10338595
OpenAlexW4376598514

What OpenQuestion holds

Textmetadata
LicenceTDM
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.